Ion channel regulation

Wickman K, Clapham DE (1995) Ion channel regulation by G proteins. Physiol Rev 75 865-85... 

Ion channels - regulated by membrane potential or ligands - provide and support complex signalling processes in nerve cells, surrounded by membranes that act as insulators all the way down the signal flow to the target or as communicators at the synapses. We have learned to interfere with these processes with modern therapeu-... 

Neurotransmitter release Energy metabolism Ion channel regulation... 

To further emphasize the double face (Janus face) of the molecule, it has been recently demonstrated that the transfer of a NO group to cysteine sulfhydryls on proteins, known as S-nitrosylation, is a ubiquitous regulatory reaction. It represents a form of redox modulation in diverse tissues. Nitrosylated proteins are relevant in many processes ranging from signal transduction, DNA repair, host defence, and blood pressure control to ion channel regulation and neurotransmission [56]. 

Intracellular nucleotides play an important role in enzyme and ion channel regulation as well as in energy metabolism and nucleic acid synthesis. There is now widespread appreciation that ATP (and other nucleotides) may so be released into the extracellular fluid by exocytosis from nerve terminals or secretory cells. Thus, extracellular ATP can act as a neurotransmitter or modulator in a variety of peripheral tissues and cells, in autonomic ganglia and in the central nervous system [1-3]. The responses to extracellular ATP are mediated via membrane-bound receptors, termed P2-purinoceptors. Evidence has accumulated indicating heterogeneity of P2-purinoceptors, and it has become apparent that ATP acts on at least five P2-purinoceptor subtypes, i.e. P2X> P2Y> P2U> 2T 2Z... 

Voltage-gated ion channels Transmembrane ion channels regulated by changes in membrane potential... 

CaM kinase II is a ubiquitous serine/threonine protein kinase. Fonr similar isoforms of CaM kinase II (a, P, y and 8) can be found, each encoded by distinct genes (Rostas and Dunkley, 1992 Braun and Schulman, 1995 Bayer et al., 1999). The a and P isoforms are brain specific, whereas the y and 5 forms are ubiquitous, which suggests there are functional differences between the isoforms. CaM kinase II is highly abundant in brain and is a major constituent of the postsy-naptic density (Kelly et al., 1984). It plays important roles in the synthesis and release of neurotransmitters, ion-channel regulation, structural modification of the cytoskeleton, axonal transport, synaptic plasticity, and gene expression (Braun and Schulman, 1995). 

Although not as universally important as ATP, GTP is involved in many essential body processes such as cellular signalling, protein synthesis and ion channel regulation. 

As an example, we consider the oldest and most powerful method for single-molecule kinetic analysis, the patch clamp analysis of ion-channel proteins. Ion channels regulate the flow of simple ions such as Na, K, and Ca across cell membranes. Movement of ions is equivalent to electrical current, and we have very sensitive methods for detecting electrical currents. If we take a small glass pipette and insert it into a membrane just right, we can electrically insulate the patch of membrane inside the pipette from the rest of the world. If done properly, a single ion channel will be in the patch, and we can watch... 

Ion channels regulate ion currents and electrochemical potentials across plasma membranes, which are responsible for excitabiUty of nerve, muscle and other type of cells. Single channel current recording using the patch clamp method has revealed electric properties of many kinds of channels at a single... 

Fig. 3.5. Different modalities of ion channel regulation by non-esterified arachidonate in animal cells.

Polyamine block of Kir channels is an essential physiological mechanism of ion channel regulation that is distinct from the more commonly studied roles of polyamines in cell growth and proliferation. Intracellular polyamines enter the Kir channel pore at depolarized voltages, causing preferential blockade of outward K currents and allowing cellular electrical excitation to proceed. Recently identified mutations of the Kir2.1 channel cause disruption of polyamine block and are linked to cardiac arrhythmias. 

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