Ion Channels

The cytosolic Ca2+ serves an intracellular mediator for many extracellular signals. The receptors coupling via heterotrimeric G proteins to different …

The voltage-gated Cl– channel (CLC) family in mammals contains at least nine different genes, encoding the Cl– channels CLC-Ka (CLC-K1), …

The ability of excitable cells to generate rhythmic, spontaneously firing action potentials is called pacemaking. In heart, pacemaking is accomplished by rhythmic discharge of the sinoatrial node (SA node). The firing rate is determined by a specific current slowly depolarizing a membrane to the threshold level, triggering the action potential. The ionic conductance underlying the cardiac pacemaking was identified over 20 years ago and termed I_f (f for funny)^{1, 2}. At the same time, a similar current was described in neurons and in retina, termed, respectively, I_h (h for hyperpolarization-activated) and I_q (q for queer)². The unique features of I_f/I_h/I_q current are: (1) its activation by hyperpolarization; (2) conductance of Na⁺ and K⁺ ions (K⁺/Na⁺ ~3-4); (3) blocking by low concentration (0.1-5 mM) of extracellular Cs⁺; (4) enhancement by cyclic AMP

The mechanism of water movement across cell membranes remained unclear until 1992, when the first water specific channel was identified …

An important family of membrane associated guanylate kinase proteins (MAGUK) are abundantly found in brain. They are also called SAP (synapse associated proteins) because of their location at synapses. The four identified members of this family (PSD95, CHAPSYN110, SAP102, SAP97) have three similar domains (PDZ) at N-terminus. At C-terminus, they have one SH3 domain as well as a guanylate kinase-like sequence. PDZ (PSD95-Dlg-Zo-1) domains are found in hundreds of proteins in various cells and tissues. The archetype of the MAGUK family, PSD95, which is found in brain synapses has been widely studied. Its X-ray structure shows a globular protein in which the C- and N-terminus are closed^1,2. Studies reported interactions between a C-terminal tripeptide motif of T/SXV of NMDA receptor and PSD95^3,4,5 or other SAP

Voltage-gated calcium (Ca_V) channels play a major role in the normal functioning and pathophysiology of neurons and other excitable cells. Their role includes supply of Ca²⁺ for transmitter release, regulation of excitability by activation of Ca²⁺-dependent currents and activation of other Ca²⁺-dependent processes, including control of gene expression. Since Ca²⁺ entry regulates so many cellular processes, the correct trafficking and localization of Ca_V channels is of great importance for the normal functioning of cells.

Recently, mutations in a number of genes, causing disease in humans and mice, have been implicated in the context of voltage dependent ion channels and termed

TRP channels are a large family (20 genes) of plasma membrane, non-selective cationic channels that are either specifically or ubiquitously expressed in excitable and non excitable cells. These proteins are divided into three main subfamilies on the basis of sequence homology; TRPC, TRPV and TRPM1 (see Table). Like the K_V channel family, the TRP family can also form heteromers consisting of different members of the same subfamily. Their non-selective cationic nature makes them depolarizing agents, while their calcium permeability makes them as transducers leading to [Ca²⁺]_in elevation. However, there are many different gating mechanism and/or modulating agents that activate and inactivate different members of this channel family (for reviews see^2,3).