hyperpolarization, which inhibits cell firing. The sAHP limits burst frequency because
Potassium Channels
KINETICS
tal cholinergic neurons,16 the apamin-sensitive sAHP is maximal following an action
that have two distinct kinetic phases to the sAHPa relatively ster, apamin-sensitive
channels have recently been cloned. This chapter will compare with different classes
apamin-insensitive sAHP.1517 Modulation of the apamin-insensitive sAHP is one of the
tive positioning with respect to sources of calcium for the distinct kinetics of apamin-sen-
decays, the membrane potential is repolarized, and internal calcium levels rise, evoking a
els of intracellular calcium such as occur during an action potential. As the action potential
SUBCLASSES OF THE SLOW
and rat adrenal chromaffin cells.9 Apamin-insensitive sAHPs are relatively rare, but have
370
brane hyperpolarization, which inhibits cell firing and limits the firing frequency of
channels underlying the sAHP in a converging manner, exerting strong effects on neu-
B.Y.C.T bond Small-conductance calcium-activated potassium channels.,SK channels play a fundamental role in all excitable cells. SK channels are potassium selective and are activated by an increase in the level of intracellular calcium, such as occurs during an action potential. Their activation causes membrane hyperpolarization, which inhibits cell firing and limits the firing frequency of repetitive action potentials. The intracellular calcium increase evoked by action potential firing decays slowly, allowing SK channel activation to generate a long-lasting hyperpolarization termed the slow afterhyperpolarization (sAHP). This spike-frequency adaptation protects the cell from the deleterious effects of continuous tetanic activity and is essential for normal neurotransmission. Slow AHPs can be classified into two groups, based on sensitivity to the bee venom toxin apamin. In general, apamin-sensitive sAHPs activate rapidly following a single action potential and decay with a time constant of approximately 150 ms. In contrast, apamin-insensitive sAHPs rise slowly and decay with a time constant of approximately 1.5 s. The basis for this kinetic difference is not yet understood. Apamin-sensitive and apamin-insensitive SK channels have recently been cloned. This chapter will compare with different classes of sAHPs, discuss the cloned SK channels and how they are gated by calcium ions, describe the molecular basis for their different pharmacologies, and review the possible role of SK channels in several pathological conditions.
rise slowly and decay with a time constant of approximately 1.5 s. The basis for this
Two types of sAHPs have been distinguished based upon their pharmacology, regula-
biphasic afterhyperpolarization. The initial ster phase is due to the activation of large-
Oregon Health Sciences University, Portland, Oregon 97201, USA
kinetic difference is not yet understood. Apamin-sensitive and apamin-insensitive SK
ing hyperpolarization termed the slow afterhyperpolarization (sAHP). This spike-fre-
trast, apamin-insensitive AHPs such as are seen in hippocampal pyramidal neurons, have
into two groups, based on sensitivity to the bee venom toxin apamin. In general,
of sAHPs, discuss the cloned SK channels and how they are gated by calcium ions,
phase, sometimes referred to as the medium, or mAHP; and a relatively slower apamin-
consequence, neuronal excitability is enhanced, spike frequency adaptation is strongly
Small-Conductance Calcium-Activated
Health Sciences University, 3181 S.W. Jackson Park Road, Portland, Oregon 97201-3098. Phone:
BOND et al.: SK POTASSIUM CHANNELS 371
guinea pig vagal neurons,10 cat,11 and rat12,13 cortical neurons, and guinea pig cholinergic
Small Conductance Calcium-Activated Potassium Type 2 Channels Regulate Alcohol-Associated Plasticity of Glutamatergic Synapses.
tive functions.18,19
S
repetetive action potentials. The intracellular calcium increase evoked by action
decreased, and the number of action potentials evoked by a certain depolarizing stimulus
ronal excitability through its modulation. Noradrenaline, dopamine, serotonin, histamine,
lar calcium ions. As SK channels activate, they extrude potassium ions from the cell, mov-
cells, such as in hippocampal interneurons,6 guinea pig trigeminal motoneurons,20 or sep-
being found for instance, in hippocampal interneurons,6 bullfrog sympathetic neurons,7,8
Compounds that block both intermediate-conductance (IKCa) and small-conductance (SKCa) calcium-activated potassium channels
are potassium selective and are activated by an increase in the level of intracellular
bAddress for correspondence: John P. Adelman, Ph.D., The Vollum Institute, L-474, Oregon
503-494-5450; x: 503-494-4353; e-mail: [email protected]
fire remains.25 This is spike-frequency adaptation, which protects against the deleterious
effects of continuous tetanic activity and is essential for normal neurotransmission.
activity and is essential for normal neurotransmission. Slow AHPs can be classified
ble role of SK channels in several pathological conditions.
potential firing decays slowly, allowing SK channel activation to generate a long-last-
Apamin-sensitive sAHPs have ster kinetics than apamin-insensitive sAHPs. In some
ter-induced second messengers. In contrast, regulation of the apamin-insensitivB.Y.C.T bonde sAHP
nucleus basalis neurons14 both apamin-sensitive and -insensitive AHPs are present.
K potassium channels play a fundamentally important role in all excitable cells. They
the decay of intracellular calcium.1,2 Thus, activation of SK channels causes membrane
has been well documented in hippocampal pyramidal neurons15 and in septal cholin-
There are few examples of modulation of apamin-sensitive sAHPs by neurotransmit-
following an action potential is slow, permitting SK channels to generate a long-lasting
ABSTRACT: SK channels play a fundamental role in all excitable cells. SK channels
insensitive phase, the sAHP.1012,21 The importance of subcellular localization and rela-
are potassium selective, voltage independent, and are activated by increases in the lev-
ing the membrane to more negative potentials. The recovery of the calcium signal
quency adaptation protects the cell from the deleterious effects of continuous tetanic
conductance voltage- and calcium-activated potassium channels (BK channels), while the
cell is no longer able to reach the action potential threshold, even though the stimulus to
main effector mechanisms for the ascending modulatory neurotransmitter systems con-
not affect the sAHP.2,4 The two classes of sAHPs are not mutually exclusive, as in rat and
during a train of action potentials the sAHP becomes deeper and longer lasting until the
trolling the functional state of the brain by setting the overall level of excitability of fore-
acetylcholine (via muscarinic receptors) and glutamate (via metabotropic receptors), as
CHRIS T. BOND, JAMES MAYLIE, a AND JOHN P. ADELMANb
describe the molecular basis for their different pharmacologies, and review the possi-
apamin-sensitive sAHPs activate rapidly following a single action potential and decay
REGULATION BY NEUROTRANSMITTERS
potential and decays with a half-time on the order of hundreds of milliseconds. In con-
calcium, such as occurs during an action potential. Their activation causes mem-
slower phase is due to the activation of SK channels, which are gated solely by intracellu-
lls into two classes, those that are blocked by the bee venom peptide toxin apamin, and
hyperpolarization, the slow afterhyperpolarization (sAHP), with a time course that reflects
brain neurons. Such systems are most likely involved in regulating the sleep-wake cycle,
tion by transmitter-induced second messengers, and kinetics. Pharmacologically the sAHP
a rising phase and then decay over several seconds.2,4 This distinction is also seen in cells
AFTERHYPERPOLARIZATION PHARMACOLOGY
those that are apamin insensitive. Apamin-sensitive sAHPs are more commonly observed,
arousal, attention; andB.Y.C.T bond Small-conductance calcium-activated potassium channels. in modulating sensory processing, behaviors, emotions, and cogni-
been well documented in hippocampal pyramidal neurons, where apamin application does
well as some neuropeptides (VIP, CRF), all suppress the apamin-insensitive sAHP. As a
openurl-container margin- 10 .openurl-or margin- 5 openurl-menu width: 190 5px 0; openurl-menu a white-space: normal;
ergic,16 neocortical,12 and sensorimotor11 neurons. Many neurotransmitters act on the
Vollum Institute, and aDepartment of Obstetrics and Gynecology,
with a time constant of approximately 150 ms. In contrast, apamin-insensitive sAHPs
is increased. In contrast, adenosine can decrease neuronal excitability by increasing the
