Channels and Signal Transduction Pathways in Neurons
Potassium (K⁺) channels constitute the most diverse class of ion channels; these channels are especially important for regulation of the neuronal excitability and provide signaling activity in a variety of ways. These channels are major determinants of the membrane excitability, influencing th...
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Інститут фізіології ім. О.О. Богомольця НАН України
2015
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| Цитувати: | Potassium Channels and Signal Transduction Pathways in Neurons / I.S. Magura, N.A. Bogdanova, E.V. Dolgaya // Нейрофизиология. — 2015. — Т. 47, № 1. — С. 81-86. — Бібліогр.: 35 назв. — англ. |
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irk-123456789-1481542019-02-18T01:23:04Z Channels and Signal Transduction Pathways in Neurons Magura, I.S. Bogdanova, N.A. Dolgaya, E.V. Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) Potassium (K⁺) channels constitute the most diverse class of ion channels; these channels are especially important for regulation of the neuronal excitability and provide signaling activity in a variety of ways. These channels are major determinants of the membrane excitability, influencing the resting potential of the membranes, waveforms and frequencies of action potentials, and thresholds of excitation. Voltage-gated K⁺ channels do not exist as independent units merely responding to changes in the transmembrane potential; these are macromolecular complexes able to integrate a great variety of cellular signals that provide fine tuning of channel activities. Compounds that change K⁺ channel properties are commonly employed as therapeutic agents in a number of pathologies, in particular, arrhythmias, cancer, and neurological disorders (psychoses, epilepsy, stroke, and Alzheimer’s disease). Калієві канали виконують важливі функції у великій кількості шляхів передачі клітинних сигналів у нервовій системі. Складна обробка та інтеграція сигналів, котрі спостерігаються у нейронах, полегшуються через наявність великого набору воротних властивостей іонних каналів, зокрема, таких властивостей потенціалкерованих калієвих каналів. Специфічні сполучення калієвих каналів забезпечують нейронам широкий репертуар характеристик збудливості та надають змогу кожному нейрону відповідати специфічним чином на дію конкретного вхідного сигналу в конкретний момент часу. Властивості багатьох калієвих каналів можуть модулюватися від дією шляхів вторинних месенджерів, активованих нейротрансмітерами та стимулами інших видів. Калієві канали формують найбільш різноманітний клас іонних каналів. Ці канали суттєво важливі для регуляції збудливості нейронів і сигнальної активності, що здійснюється різним чином. Дані канальні структури є основними детермінантами збуливості мембрани, впливаючи на потенціал спокою мембран, форму та частоту потенціалів дії та пороги збудження. Потенціалкеровані калієві канали не існують як незалежні одиниці, в основному відповідальні за зміну мембранного потенціалу; це макромолекулярні комплекси, здатні інтегрувати колосальну кількість клітинних сигналів, котрі реалізують тонку настройку активності каналів. Сполуки, котрі змінюють властивості калієвих каналів, широко використовуються як терапевтичні агенти в таких випадках, як аритмії, ракові захворювання та неврологічні розлади (психози, епілепсія, інсульти та хвороба Альцгеймера). Цілями значної кількості терапевтичних агентів є канали, що не відносяться до калієвих, але "ненавмисно" блокують саме калієві канали. Таке блокування калієвих каналів може зумовлювати потенційно дуже серйозні або навіть смертельні побічні ефекти. 2015 Article Potassium Channels and Signal Transduction Pathways in Neurons / I.S. Magura, N.A. Bogdanova, E.V. Dolgaya // Нейрофизиология. — 2015. — Т. 47, № 1. — С. 81-86. — Бібліогр.: 35 назв. — англ. 0028-2561 http://dspace.nbuv.gov.ua/handle/123456789/148154 576.314.6 en Нейрофизиология Інститут фізіології ім. О.О. Богомольця НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) |
| spellingShingle |
Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) Magura, I.S. Bogdanova, N.A. Dolgaya, E.V. Channels and Signal Transduction Pathways in Neurons Нейрофизиология |
| description |
Potassium (K⁺) channels constitute the most diverse class of ion channels; these channels
are especially important for regulation of the neuronal excitability and provide signaling
activity in a variety of ways. These channels are major determinants of the membrane
excitability, influencing the resting potential of the membranes, waveforms and frequencies
of action potentials, and thresholds of excitation. Voltage-gated K⁺ channels do not exist as
independent units merely responding to changes in the transmembrane potential; these are
macromolecular complexes able to integrate a great variety of cellular signals that provide
fine tuning of channel activities. Compounds that change K⁺ channel properties are commonly
employed as therapeutic agents in a number of pathologies, in particular, arrhythmias, cancer,
and neurological disorders (psychoses, epilepsy, stroke, and Alzheimer’s disease). |
| format |
Article |
| author |
Magura, I.S. Bogdanova, N.A. Dolgaya, E.V. |
| author_facet |
Magura, I.S. Bogdanova, N.A. Dolgaya, E.V. |
| author_sort |
Magura, I.S. |
| title |
Channels and Signal Transduction Pathways in Neurons |
| title_short |
Channels and Signal Transduction Pathways in Neurons |
| title_full |
Channels and Signal Transduction Pathways in Neurons |
| title_fullStr |
Channels and Signal Transduction Pathways in Neurons |
| title_full_unstemmed |
Channels and Signal Transduction Pathways in Neurons |
| title_sort |
channels and signal transduction pathways in neurons |
| publisher |
Інститут фізіології ім. О.О. Богомольця НАН України |
| publishDate |
2015 |
| topic_facet |
Материалы VI Конгресса Украинского общества нейро- наук, посвященного 90-летию со дня рождения академика П. Г. Костюка (Киев, 4 – 8 июня 2014 г.) |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/148154 |
| citation_txt |
Potassium Channels and Signal Transduction Pathways in Neurons / I.S. Magura, N.A. Bogdanova, E.V. Dolgaya // Нейрофизиология. — 2015. — Т. 47, № 1. — С. 81-86. — Бібліогр.: 35 назв. — англ. |
| series |
Нейрофизиология |
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2025-07-12T18:28:21Z |
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| fulltext |
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 1 81
UDC 576.314.6
I. S. MAGURA,1 N. A. BOGDANOVA,1 and E. V. DOLGAYA1
POTASSIUM CHANNELS AND SIGNAL TRANSDUCTION PATHWAYS IN NEURONS
Received June 25, 2014
Potassium (K+) channels constitute the most diverse class of ion channels; these channels
are especially important for regulation of the neuronal excitability and provide signaling
activity in a variety of ways. These channels are major determinants of the membrane
excitability, influencing the resting potential of the membranes, waveforms and frequencies
of action potentials, and thresholds of excitation. Voltage-gated K+ channels do not exist as
independent units merely responding to changes in the transmembrane potential; these are
macromolecular complexes able to integrate a great variety of cellular signals that provide
fine tuning of channel activities. Compounds that change K+ channel properties are commonly
employed as therapeutic agents in a number of pathologies, in particular, arrhythmias, cancer,
and neurological disorders (psychoses, epilepsy, stroke, and Alzheimer’s disease).
Keywords: potassium channels, signal function, neurological disorders.
INTRODUCTION
It is clear that the impact
of ion channel research on our
understanding of the nervous
system is only starting. (F.Bezanilla, 2008).
Academician Platon Kostyuk in his monograph
published by the Physiological Society (“Plasticity in
nerve cell function,” 1998) demonstrated that the most
unique feature of the nervous system can probably
be described as plasticity. For years, long-lasting
plasticity of synaptic transmission was the favorite
mechanism to account for information storage in the
brain. Calcium signals participate in an extremely
complicated intracellular machinery that is capable
of controlling structural and functional properties
of the neurons [1-3]. Recent evidence indicates that
the neuronal message is also persistently filtered
through regulation of the functioning of voltage-
gated ion channels. Changes in the expression level
or biophysical properties of ion channels may alter a
large range of functional processes such as dendritic
integration, spike generation, signal propagation via
the dendritic and axon, and regulation of the plasticity
thresholds [4-7].
Potassium channels (K+ channels) have at present
been identified in virtually all types of cells in all or-
ganisms where they are involved in a great variety of
physiological functions. These channels are ubiquitous
and critical for life. They are found in Archaebacte-
ria, Eubacteria, and eukaryotic cells, both plant and
animal; their amino acid sequences can be very eas-
ily recognized because K+ channels always contain a
highly conservative segment called the K+ channel sig-
nature sequence. This sequence forms a structural el-
ement known as the selectivity filter; it prevents pas-
sage of Na+ ions but allows K+ ions to move through
the membrane at rates approaching that of the diffu-
sion limit. The K+ selectivity filter catalyses dehydra-
tion, transfer, and rehydration of a K+ ion within about
ten nanoseconds. This physical process is absolutely
crucial for the production of electrical signals in bi-
ology. Within a certain time interval, the selectivity
filter contains two K+ ions about 0.75 nm apart. This
configuration promotes the ion conduction by exploit-
The article is dedicated to the 90th anniversary of
the outstanding Ukrainian physiologist academician
Platon Kostyuk, who devoted himself to ion channel
research.
Матеріали VI Конгресу Українського товариства нейронаук, присвяченого 90-й
річниці з дня народження академіка П. Г. Костюка (Київ, 4 – 8 червня 2014 р.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 182
I. S. MAGURA, N. A. BOGDANOVA, and E. V. DOLGAYA
ing electrostatic repulsive forces to overcome attrac-
tive forces between K+ ions and the selectivity filter.
The architecture of the channel pore determines the
physical principles underlying selective K+ conduction
[1-4]. This is the hallmark of K+ channels, namely the
nearly perfect selectivity for K+ ions over Na+ ions in
the setting of very high K conduction rates. In some
members of the family of voltage-gated K+ channels,
the removal of internal and external K+ allows Na+
ions to permeate through the pore [8-12].
POTASSIUM CHANNELS AND
INTEGRATION OF THE SIGNALS IN
NEURONS
Effective control over the phenotype of individual
neurons is based on the regulation of transcription
and translation of the relevant genes, and such control
is provided perfectly. Many types of channels and
receptors are expressed in units of the nervous system,
contributing to the complex and diverse functional
repertoires of functioning of the neurons [12]. Complex
processing and integration of the signals observed in
neurons are facilitated by a variety of gating properties
of different ion channels, particularly of those of
voltage-gated K+ channels [6].
Potassium (K+) channels form the most diverse class
of the ion channels. These channels are crucially im-
portant for the regulation of neuronal excitability and
for the formation of signaling activity in a variety of
ways. These channel structures are major determi-
nants of the membrane excitability; they influence the
resting potential on the membranes and modulate the
waveforms and frequencies of action potentials (APs)
and thresholds of excitation. Voltage-gated K+ chan-
nels are key components of multiple signal transduc-
tion pathways. The functional diversity of K+ channels
is much more extensive than the molecular diversity
of the respective class of the genes. A distinctive com-
bination of K+ channels endows neurons with a broad
repertoire of the excitation properties and allows each
neuron to respond in a specific manner to a given input
within a given time interval. The properties of many
channels can be modulated by second messenger path-
ways activated by neurotransmitters and other types of
stimuli. Potassium channels are among the most fre-
quent targets for the actions of several signaling sys-
tems [11-14].
The diversity of different members of the K+ chan-
nel family is related mainly to various ways in which
K+ channels come from the closed state to the open
one. Some K+ channels are ligand-gated, which means
that pore opening is energetically coupled with an
ion, a small organic molecule, or even a protein mole-
cule. Other K+ channels are voltage-gated; in this case,
opening is energetically coupled to the movement of a
charged voltage sensor within the membrane electric
field. Therefore, different kinds of K+ channels open
in response to different stimuli, namely to changes in
the intracellular Ca2+ concentration, to levels of cer-
tain G-protein subunits in the cell, or to a value of the
membrane voltage.
The specificity of information is generally encoded
by the kinetics of the frequency, duration, bursting,
and summation of APs. A neuron (or a specific axon,
or a dendrite), when it is necessary to change its fir-
ing pattern, can rapidly regulate the gating behavior of
the existing channels. If longer-term modifications of
the firing patterns are required, the cell may alter the
transcriptional expression of the ion channel genes for
providing diverse functions. The number of K+ channel
genes is relatively large; the diversity of endogenous
K+ current phenotypes observed in various excitable
cells is, however, much greater. Additional process-
es such as alternative splicing, posttranslational modi-
fication, and heterologus assembling of pore-forming
subunits in tetramers contribute to extend the function-
al diversity of a limited repertoire of the K+ channel
gene products. Even greater diversity can be achieved
through interactions between K+ channel proteins and
accessory proteins or subunits [15-19].
General mechanisms of ion channel targeting are of
considerable interest. Historically, targeting and cel-
lular localization of K+ channels were believed to be
primarily related to protein-protein interactions. How-
ever, there is increasing interest in the potential role of
cellular lipids in the regulation of K+ channel localiza-
tion, which was determined by a revised view on the
membrane organization. The traditional fluid mosaic
model has been modified to reflect the developing ap-
preciation on the membrane lipid heterogeneity. The
existence of membrane microdomains, particularly
those referred to as lipid rafts, has motivated investi-
gators to examine the role of protein–lipid interactions
in the ion channel localization more closely. Lipid
rafts are specialized membrane microdomains rich in
sphingolipids and cholesterol. These rafts have been
implicated in the organization of many membrane-as-
sociated signal pathways. Biochemical and functional
studies indicated that Kv channels are in close spatial
relations with lipid raft microdomains on the cell sur-
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 1 83
POTASSIUM CHANNELS AND SIGNAL TRANSDUCTION PATHWAYS IN NEURONS
face [15].
Precise control of the neuronal AP patterns underlies
the basic functioning of the central and peripheral
nervous systems. This control relies, to a significant
extent, on the adaptability of voltage-gated potassium,
sodium, and calcium channels. The importance of
voltage-gated ion channels in mediating and sculpting
electrical signals in the brain is well established.
Theoretical and experimental reports described how
neurons can respond to changing inputs by adjusting
their firing properties, and these events are mediated
by modification of voltage-gated ion channels [5].
Recently obtained evidence indicates that neuronal
output messages are persistently filtered through
regulation of voltage-gated ion channels [14]. There
are many genes encoding the pore-forming subunits
of the “classical” voltage-gated ion channels in
mammalian neurons.
Complex processing and integration of the signals
observed in neurons are facilitated by a diverse range
of the gating properties of ion channels typical of this
cell type, particularly of those of the voltage-gated K+
channels. Distinctive combinations of ion channels
endow neurons with a broad repertoire of excitation
properties and allow each neuron to respond in a spe-
cific manner to a given input at a given moment. The
properties of many K+ channels can be modulated by
second messenger pathways activated by neurotrans-
mitters and other stimuli.
It is now widely recognized that voltage-gated K+
channels exist not as independent units merely re-
sponding to changes in the transmembrane potential
but as macromolecular complexes able to integrate an
enormous multiplicity of cellular signals providing
fine tuning of channel activities. Proteins associated
with K+ channels may do so dynamically with regu-
lated on- and off- rates, or they may be constitutive
components of the complexes determining the life-
time of the channel protein. The functional results of
interactions with these accessory proteins include al-
teration of the channel assembling, trafficking, pro-
tein stability, gating kinetics, conduction properties,
and responses to signal transduction events [17]. Al-
though a single type of the K+ channel α subunit is of-
ten present in a variety of different organs, the kinet-
ic behavior and conformational changes of α subunits
can be modulated by co-assembling with an ancillary
subunit. The expression of ancillary subunits varies
between organs, as well as between regions of one and
the same organ [19]. This diversity of the ancillary
subunit expression, therefore, contributes to the
diverse assortment of potassium currents recorded
from native tissues. In addition, relative expression of
K+ channels and their associated ancillary subunits can
be affected by a number of factors. The latter change
in the course of development, with modifications of
the hormonal state, under ischemic conditions, etc.,
these factors also modulate the electrophysiology
and pharmacology of native potassium currents [17].
Potassium channels encompass numerous auxiliary
subunits, and many channels can be assembled with
heteromers of multiple subunits and splice variants,
rendering the combinatorial diversity of voltage-gated
ion channels truly staggering [6].
Potassium currents contribute in a diverse mode to
the specificity of neuronal firing patterns. The compo-
sition of these currents may be determined by regulat-
ed transcription, alternative RNA splicing, and post-
translational modifications. Alternative splicing is
obvious in nearly all metazoan organisms as a means
for producing functionally diverse polypeptides from
a single gene [16].
As is generally accepted, a neuron can be divided
into three interrelated modules, namely the input, in-
tegration core, and output. Historically, voltage-gat-
ed ion channels were postulated to play a crucial role
at the output part of the neuron. A passive integrator
feeds an algebraic sum of inputs of the neuron to a
nonlinear integrating device (cell body), which fires
APs depending on the inputs it receives. The role of
various voltage-gated ion channels in modulating sin-
gle APs and their bursts have been teased apart, and
significant information is available on the activa-
tion, deactivation, and inactivation dynamics of var-
ious ion channels within millisecond-order time in-
tervals. Later on, equipped with the knowledge that
there are conductances active in the subthreshold
states and that neuronal dendrites possess the respec-
tive ion channels, the role of voltage-gated channels in
the integration module began to attract special atten-
tion. Experimental and theoretical evidence is being
accumulated on how ion channels could contribute to
integration of synaptic inputs localized on and outside
of the dendrites or to back-propagating APs [18, 20].
Potassium channels located in the dendrites of hippo-
campal CA1 pyramidal neurons control the shape and
amplitude of back-propagating APs, the amplitude of
excitatory input effects, and the dendrite excitabil-
ity. Non-uniform gradients in the distribution of K+
channels on the dendrites make the dendritic electri-
cal properties markedly different from those found in
the soma [21].
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 184
I. S. MAGURA, N. A. BOGDANOVA, and E. V. DOLGAYA
Ion channels are not only crucial in neurons of
healthy individuals; several types of these channels
have been implicated in the pathogenesis of certain
diseases, both genetic and acute. The successfulness
of searching for possible treatments of channel-asso-
ciated diseases will be higher if we understand in de-
tail how channels, including K+ ones are implicated
in physiology of the cell and if we will be able to de-
sign modifications that restore normal functions of the
channels [10]. For example, several human genetic
diseases involving cardiac arrhythmias, deafness, epi-
lepsy, diabetes, and misregulation of the blood pres-
sure, are caused by disruptions of the K+ channel genes
[9].
The K+ channel activity is modulated by external
and internal K+ ions. Elevation of the [K+]O may occur
just through high levels of neuronal activity and
through specific actions of neurotransmitters on glial
cells. Some of the effects of changes in the [K+]O can
be attributed to shifts in the K+ equilibrium potential,
which modify both the resting potential in the cells
and the driving force for K+ currents. Variations
in the [K+]O are implicated in the pathogenesis of a
few disorders, including epileptiform seizures and
electrical instability of the heart following acute
ischemia. These changes might occur through [K+]O-
determined modulation of K+ channels and changes in
the firing pattern of the neuron due to shifts in the [K+]
O [9].
Two distinct molecular mechanisms for K+ chan-
nel inactivation have been described. These are an
N-type mechanism related to rapid occlusion of the
open channel by an intracellular tethered blocker, and
a slow C-type mechanism involving a slower change at
the extracellular mouth of the pore. These two mecha-
nisms should be coupled in some a way [22]. Recent
experiments showed that slow C-type inactivation can
be further divided into P-type and C-type. Slow in-
activation of K+ channels can be strongly influenced
by permeating ions. Cumulative inactivation of volt-
age-regulated K+ channels is thought to be due to the
P/C-type inactivation state, the recovery from which
is slow [23-25]. Cumulative inactivation of K+ chan-
nels appears to be state-dependent and voltage-inde-
pendent. Cumulative inactivation, similar in its mech-
anisms to that of K+ channels, is manifested in Ca2+
channels [26]. One of the main causes of the frequen-
cy-dependent spike broadening during repetitive dis-
charges is cumulative inactivation of certain K+ chan-
nels. Such AP broadening can modify a few aspects of
neuronal signaling [27-29].
Tetraethylammonium (TEA) ions have been for
many years used as effective probes in the research
of the structure and functions of K+ channels. This is,
perhaps, due to the fact that TEA ions are positively
charged (similarly to K+ ions) and have about the same
size as hydrated K+ ions. External TEA blocks many
types of K+ channels, but within an about 1000-fold
range of effective concentrations [30-31]. This differ-
ence can mostly be attributed to certain amino acid
residue at a single position in the outer entrance to the
pore [32]. Results of recent molecular dynamic simu-
lations and electrostatic calculations allowed research-
ers to suggest that the external TEA binding site in K+
channels is localized outside with respect to the mem-
brane electric field. The TEA-binding site is formed by
a bracelet-like complex of pore-lining aromatic resi-
dues. The center of the bracelet can bind a TEA ion via
a cation-π orbital interaction [30-31, 33].
The K+-dependent conformational alteration that re-
sulted in a change in the [TEA]O potency correlates
with the effect of K+ on the inactivation rate. As the
[K+]O increased, the [TEA]O potency and inactivation
rate also increased. The effects of [K+]O on еру inacti-
vation rate became saturated at the same value of [K+]O
as the effect on the [TEA]O potency did. These results
suggest that different channel conformations associat-
ed with different [TEA]O potencies can affect the rate
of slow inactivation. The selectivity filter is an inte-
gral part of the inactivation mechanisms. The selectiv-
ity filter is the site through which K+ ions influence the
channel conformation [31, 34, 35].
Potassium channels mediate outward K+ currents
and increase the membrane conductance; they tend to
hyperpolarize the cell membrane and attenuate the ef-
fects of excitatory stimuli. Potassium channels are,
therefore, normally regarded as inhibitory, i.e., they
reduce the neuronal excitability. Genetically provoked
suppression of K+ channel activity in mice causes the
development of epileptiform activities. Pharmaco-
logical blocking of K+ channels, e.g., with 4-amino-
pyridine or barium, readily evokes epileptic seizures.
Compounds having K+ channel blocking properties
are commonly employed as therapeutic agents for a
number of conditions such as arrhythmias, cancer, and
neurological disorders, including psychoses, epilepsy,
stroke, and Alzheimer’s disease. There is a wide va-
riety of therapeutic agents targeted to non-K+ chan-
nels but providing an unintended block of K+ chan-
nels. This type of K+ channel blocking can result in
potentially serious and sometimes even fatal side ef-
fects (e.g., in the case of cardiac arrhythmias) [17].
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 1 85
POTASSIUM CHANNELS AND SIGNAL TRANSDUCTION PATHWAYS IN NEURONS
CONCLUDING REMARKS
Regulation of transcription and translation of the
relevant genes exerts significant control effects on
the phenotype of individual neurons. Many types
of channels and receptors contributing to diverse
functional repertoires of the neurons are expressed
in the nervous system. Complex processing and
integration of the signals observed in neurons are
facilitated by an extensive range of the gating
properties of ion channels in this cell type, particularly
of voltage-gated potassium channels.
Potassium channels form the most diverse class of
ion channels; these channels are crucially important
for the regulation of neuronal excitability and
signaling activity in a variety of modes. They are
major determinants of the membrane excitability,
influencing the resting potential on the membranes,
waveforms and frequencies of action potentials (APs),
and thresholds of excitation. Potassium channels
fulfill important functions in many signal transduction
pathways in the nervous system. Voltage-gated K+
channels are key components of a number of signal
transduction pathways in the cell. The functional
diversity of these channels exceeds many times the
considerable molecular diversity of the respective
genes. Distinctive combinations of the properties of
K+ channels endows neurons with a broad repertoire
of their excitation properties and allow each neuron
to respond in a specific manner to a given input at a
given time. The properties of many channels can be
modulated by secondary messenger pathways activated
by neurotransmitters and certain other stimuli.
Potassium channels are among the most frequent
targets for the actions of several signaling systems.
Potassium channel activity is significantly modulated
by external and internal K+ ions. Significant elevation
of the [ K+ ]O may occur just through high levels of
neuronal activity and through specific actions of
neurotransmitters on glial cells [1].
The information contained in spike timing is
available immediately rather than after an averaging
integration period. Furthermore, timing of the AP
patterns can potentially transmit even more information
than timing of individual constituent spikes. If longer-
term modifications of the firing patterns are required,
the cell may alter the transcriptional expression of ion
channel genes.
The selectivity of ion channel pores has generally
been regarded as the fixed one. However, recent
studies on various classes of ion channels challenged
the generality of this idea and showed that some ion
channels can significantly modify their ion selectivity,
and normally impermeant ions begin to permeate
under some certain circumstances. This phenomenon
represents both a new functional aspect of physiology
of ion channels and allows one to propose a suggestion
on novel ways by which channels may process
information in the nervous system [35]. Ion channels
are not only crucial molecular membrane objects
in healthy individuals; some of them have been
implicated in the pathogenesis of different diseases,
either genetic or acute [19].
This publication was not associated with any experiments
on animals or tests involving human subjects; therefore, it does
not require confirmation of compliance with existing ethical
standards from this aspect.
The authors of this communication, I. S. Magura,
N. A. Bogdanova, and E. V. Dolgaya, confirm that this
publication was not associated with any conflicts regarding
commercial or financial relations, relations with organizations
and/or individuals who may have been related to the study, and
interrelations of co-authors of the article.
І. С. Магура1, Н. А. Богданова1, О. В. Довга1
КАЛІЄВІ КАНАЛИ ТА ШЛЯХИ ПЕРЕДАЧІ КЛІТИННИХ
СИГНАЛІВ В НЕЙРОНАХ
1 Інститут фізіології ім. О. О. Богомольця НАН України,
Київ (Україна).
Р е з ю м е
Калієві канали виконують важливі функції у великій кіль-
кості шляхів передачі клітинних сигналів у нервовій систе-
мі. Складна обробка та інтеграція сигналів, котрі спостері-
гаються в нейронах, полегшуються через наявність великого
набору воротних властивостей іонних каналів, зокрема та-
ких властивостей потенціалкерованих калієвих каналів. Спе-
цифічні сполучення калієвих каналів забезпечують не-
йронам широкий репертуар характеристик збудливості та
дозволяють кожному нейрону відповідати специфічним
чином на дію конкретного вхідного сигналу в конкретний
момент часу. Властивості багатьох калієвих каналів мо-
жуть модулюватися під дією шляхів вторинних месендже-
рів, активованих нейротрансмітерами та стимулами інших
видів. Калієві канали формують найбільш різноманітний
клас іонних каналів. Ці канали істотно важливі для регуля-
ції збудливості нейронів та сигнальної активності, що здій-
снюється різним чином. Дані канальні структури є основ-
ними детермінантами збудливості мембрани, впливаючи на
потенціал спокою мембран, форму та частоту потенціалів
дії та пороги збудження. Потенціалкеровані калієві канали
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 186
I. S. MAGURA, N. A. BOGDANOVA, and E. V. DOLGAYA
не існують як незалежні одиниці, в основному відповідаль-
ні за зміну мембранного потенціалу; це макромолекулярні
комплекси, здатні інтегрувати колосальну кількість клітин-
них сигналів, котрі реалізують тонку настройку активнос-
ті каналів. Сполуки, котрі змінюють властивості калієвих
каналів, широко використовуються як терапевтичні агенти
в таких випадках, як аритмії, ракові захворювання та нев-
рологічні розлади (психози, епілепсія, інсульти та хворо-
ба Альцгеймера). Цілями значної кількості терапевтичних
агентів є канали, що не відносяться до калієвих, але «нена-
вмисно» блокують саме калієві канали. Таке блокування ка-
лієвих каналів може зумовлювати потенційно дуже серйозні
або навіть смертельні побічні ефекти.
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