Channelpedia

KCa

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Introduction

KCa channels differ in their primary amino acid sequences and exhibit different single-channel conductances and pharmacological profiles. Each subtype plays a specific role in several physiological processes, including neurosecretion, smooth muscle tone, action potential shape and spike frequency adaptation [1171].
The International Union of Pharmacology has put the Ca2+- activated K+ channels into one family which can be subdivided into two functionally but genetically unrelated groups [539]) [1206]):
One group include:
•Small conductance KCa channels: KCa 2.1 (SK1), 2.2 (SK2) and 2.3 (SK3). These channels are sensitive to block by apamin (100 pM–10 nM), which distinguishes them from all other KCa channels.
•Intermediate conductance: KCa3.1 (IK)
These channels are voltage-insensitive and are activated by low concentrations of internal calcium (less than 1.0 microM). Both IK and SK channels play roles in processes involving calcium-dependent signaling in both electrically excitable and nonexcitable cells. Unless they do not bind calcium directly they detect it by virtue of calmodulin, which is constitutively bound to the C-terminal region. Binding of calcium to this calmodulin results in conformational changes that are in turn responsible for channel gating.

The other group include:
•Large conductance KCa channels (KCa1.1, also known as BK channel, Slo or Slo1), a voltage-sensitive channel that binds calcium independently of calmodulin but mediated by at least three divalent catión binding sites in the cytoplasmic carboxyl domain of each channel subunit.
•KCa4.1 (Slack or Slo2.2)
•KCa4.2 (Slick or Slo2.1)
•KCa5.1 (Slo3). The mouse Slo3 gene (KCNMA3) encodes a K(+) channel that is regulated by changes in cytosolic pH. [165]

Slack and Slick subunits form the sodium activated potassium channels.

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Gene

For a phylogenetic tree and nomenclature/classification, see Wei et al. 2005 [539]

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Kinetics

The fast after hyperpolarization (AHP), which activates rapidly and typically lasts 1–10 msec, is mediated by BK-type calcium activated potassium channels, as well as some voltage-gated potassium conductances, and is responsible for action potential repolarization. The medium AHP, which also activates rapidly, has a decay time constant of approximately 100 msec and is predominately mediated by SK channels [1107],[1216]).

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Expression and Distribution

KCa channels are widely expressed in neuronal and non neuronal tissues including epithelia, smooth muscle, and sensory cells where they couple membrane potential and intracellular calcium concentration [1209]), [1457].

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Function

KCa channels give rise to an efflux of potassium via re/hyperpolarization of the membrane potential feeds back onto intracellular calcium concentration by limiting calcium influx either through deactivation of voltage-gated calcium channels or through increased transport activity of sodium/calcium exchangers. Accordingly, KCa channels shape the amplitude and duration of calcium transients and thus affect the downstream signaling pathways that are triggered by changes in intracellular calcium concentration [1457].

Both types of KCa channels have been implicated in a variety of physiological processes:
-BK channels: regulation of smooth muscle tone, microbial killing in leukocytes, modulation of hormone and neurotransmitter release. In central neurons, contribute to repolarization of action potentials (APs) mediating the fast phase of afterhyperpolarization following an AP and influencing the release of neurotransmitters.
-SK channels: control fo uterine contractility and vascular tone, modulation of hormone secretion, control of cell volume in red blood cells, activation of microglia and lymphocytes, regulation of excitability, firing pattern, and synaptic signal transduction in central neurons. In addition, together with nicotinic acetylcholine receptors reconstitute an unusual inhibitory synapse in auditory outer hair cells [1457].

For further information about the role of the KCa channels in diseases see the Table 1 of Kuiper et al. 2012 [1454].

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Interaction

BMS-204352 (BMS) was developed as a neuroprotective drug for disease conditions such as ischemic stroke and it has been shown to have a protective effect, due to activation of big-conductance calcium-activating potassium (BKCa) channels (Gribkoff et al., 2001 [1214]; Cheney et al., 2001 [1215]; Nardi and Olesen, 2008 [1216]).

References

165

Zhang X et al. Slo3 K+ channels: voltage and pH dependence of macroscopic currents.
J. Gen. Physiol., 2006 Sep , 128 (317-36).

1107

Faber ES et al. Functions of SK channels in central neurons.
Clin. Exp. Pharmacol. Physiol., 2007 Oct , 34 (1077-83).

1207

Shi Y et al. Mitochondrial big conductance KCa channel and cardioprotection in infant rabbit heart.
J. Cardiovasc. Pharmacol., 2007 Nov , 50 (497-502).

1211

Kim EY et al. Effects of insulin and high glucose on mobilization of slo1 BKCa channels in podocytes.
J. Cell. Physiol., 2011 Sep , 226 (2307-15).

1216

Nardi A et al. BK channel modulators: a comprehensive overview.
Curr. Med. Chem., 2008 , 15 (1126-46).

1217

O'Rourke B et al. Mitochondrial ion channels: gatekeepers of life and death.
, 2005 Oct , 20 (303-15).

1218

Kang SH et al. Mitochondrial Ca2+-activated K+ channels more efficiently reduce mitochondrial Ca2+ overload in rat ventricular myocytes.
Am. J. Physiol. Heart Circ. Physiol., 2007 Jul , 293 (H307-13).

1454

Kuiper EF et al. K(Ca)2 and k(ca)3 channels in learning and memory processes, and neurodegeneration.
Front Pharmacol, 2012 , 3 (107).

1457

Berkefeld H et al. Ca2+-activated k+ channels: from protein complexes to function.
Physiol. Rev., 2010 Oct , 90 (1437-59).

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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/207/ , accessed on 2024 Dec 21


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