The action potential of the squid giant axon is formed by just two voltage- dependent conductances in the cell membrane, yet mammalian central neurons typically express more than a dozen different types of voltage-dependent ion channels. This rich repertoire of channels allows neurons to encode information by generating action potentials with a wide range of shapes, frequencies and patterns. Recent work offers an increasingly detailed understanding of how the expression of particular channel types underlies the remarkably diverse firing behaviour of various types of neurons.

The action potential in mammalian central neurons

The simplest cell-like structure, the lipid bilayer vesicle, can respond to mechanical deformation by elastic membrane dilation/thinning and curvature changes. When a protein is inserted in the lip...

Molecular basis of mechanotransduction in living cells

Ca2+-activated K+ (KCa) channels of small (SK) and intermediate (IK) conductance are present in a wide range of excitable and non-excitable cells. On activation by low concentrations of Ca2+, they open, which results in hyperpolarization of the membrane potential and changes in cellular excitability. KCa-channel activation also counteracts further increases in intracellular Ca2+, thereby regulating the concentration of this ubiquitous intracellular messenger in space and time. KCa channels have various functions, including the regulation of neuronal firing properties, blood flow and cell proliferation. The cloning of SK and IK channels has prompted investigations into their gating, pharmacology and organization into calcium-signalling domains, and has provided a framework that can be used to correlate molecularly identified KCa channels with their native currents.

Ca2+-activated K+ channels: molecular determinants and function of the SK family

http://www.utdallas.edu/~tres/plasticity2009/Sah.pdf

Channels underlying neuronal calcium-activated potassium currents

SLO channels comprise a family of high-conductance potassium channels with several distinctive features that give them the versatility to function in various cellular contexts. The authors describe the key properties and physiological roles of these channels in the nervous system.

High-conductance potassium channels of the SLO family

Calcium entry through voltage-gated calcium channels can activate either large- (BK) or small- (SK) conductance calcium-activated potassium channels. In hippocampal neurons, activation of BK channels underlies the falling phase of an action potential and generation of the fast afterhyperpolarization (AHP). In contrast, SK channel activation underlies generation of the slow AHP after a burst of action potentials. The source of calcium for BK channel activation is unknown, but the slow AHP is blocked by dihydropyridine antagonists, indicating that L-type calcium channels provide the calcium for activation of SK channels. It is not understood how this specialized coupling between calcium and potassium channels is achieved. Here we study channel activity in cell-attached patches from hippocampal neurons and report a unique specificity of coupling. L-type channels activate SK channels only, without activating BK channels present in the same patch. The delay between the opening of L-type channels and SK channels indicates that these channels are 50-150 nm apart. In contrast, N-type calcium channels activate BK channels only, with opening of the two channel types being nearly coincident. This temporal association indicates that N and BK channels are very close. Finally, P/Q-type calcium channels do not couple to either SK or BK channels. These data indicate an absolute segregation of coupling between channels, and illustrate the functional importance of submembrane calcium microdomains.

Selective activation of Ca2+ : activated K+ channels by co-localized Ca2+ channels in hippocampal neurons

The influx of calcium (Ca2+) ions through L-type channels underlies many cellular processes, ranging from initiation of gene transcription to activation of Ca2+-activated potassium channels. L-type...

Steven J. Tavalin

Papers

Selective activation of Ca2+ : activated K+ channels by co-localized Ca2+ channels in hippocampal neurons

Modulation of Single Channels Underlying Hippocampal L-Type Current Enhancement by Agonists Depends on the Permeant Ion