Sodium, Potassium, and Calcium Channels

Nerve impulses consist of a wave of transient membrane depolarisation/re-polarisation which traverses the nerve cell and is designated an action potential. As we saw in Chapter 9, Alan Hodgkin and Andrew Huxley demonstrated in 1952 that a microelectrode implanted into the giant axon (the long process emanating from the body of 

As we saw in Chapter 9, sodium channels (Nay channels) consist of a pore-forming a subunit, which is sufficient for functional expression, associated with auxiliary p subunits which modify both the kinebcs and the voltage dependence of channel gabng of the channel. Nine mammalian Nay channel isoforms are known, of which Nayl. 1 and Nayl.3 are predominantly locabsed in neuronal cell bodies and proximal dendrites, where they conbol 

The giant axon of the squid is very large, typically 0.5 mm in diameter, and the conduction velocity is about 25 m/s. During such an action potential, an influx of 3.7 pmol/cm of Na is offset by a subsequent efflux of 4.3 pmol/cm of K.  

Calcium channels (Cay channels) mediate calcium influx in neuronal cells in response to membrane depolarisation, mediating a wide range of intracellular processes such as activation of calcium-dependent enzymes, gene transcription, and neurotransmitter exocytosis/secretion. Their activity is an essential requirement for the coupling of electric signals in the neuronal plasma membrane to physiological events within the cells. Biochemical characterisation of native brain Cay channels revealed that, in addition to the large principal 

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The primary sequences of important channel peptides, such as the nicotinic acetylcholine receptors, and sodium, potassium, and calcium channels, have been determined by the innovative work of the late professor Numa and his group. " Thereafter, various structural models on the basis of empirical as well as molecular mechanics or molecular dynamics calculations were proposed " and tested by specific point mutation studies. 

The mechanism of action of anticonvulsants remains poorly characterized, both in terms of their anticonvulsant effects or their antimanic/mood stabilizing effects. They may even have multiple mechanisms of action. At the cell membrane, anticonvulsants appear to act on ion channels, including sodium, potassium, and calcium channels. By interfering with sodium movements through voltage-operated sodium... 

Many factors can interact with dmgs to make this problem worse. These include genetic factors, such as mutations in sodium, potassium and calcium channel genes that predispose people to repolarization failure [11-13]. This is the main explanation for the fact that dmgs with this side-effect have it in only a small fraction of the population. In principle, it should become possible to screen for such genetic predispositions to exclude such patients in clinical trials and to avoid treating them with drugs that interact in this way (Fig. 9.2). 

Histrionicotoxin, 342, and synthetic analog inhibition of ligand binding at sites associated with the sodium, potassium, and calcium channels in brain membrane preparations has been investigated [721]. The effects of 342 on the ion channel of central nervous system nicotinic acetylcholine receptors [722], and on post-tetanic potentiation of mouse and rat phrenic nerve diaphram preparations have been described [723]. 

Phenytoin alters the conductance of sodium, potassium, and calcium channels within the membrane of excitable cells. At therapeutic levels, the effects of the drug are mainly due to a decrease in sodium conduction. 

Outline the possible role of the 55 and 56 segments of sodium, potassium, and calcium channels as a key region of the ion channel pore. 

Several studies have observed changes in the expression of genes encoding various ion channels following SE. These include GABA receptors, sodium, potassium and calcium channels and hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels (Brooks-Kayal et al., 1998 Chen et al., 2001 Ellerkmann et al., 2003 Bernard et al., 2004). 

Synchronization of hyperexcitable neurons is dependent on ionic currents that flow through sodium, potassium, and calcium channels. Alterations in ion channels are seen in both animal models and surgically resected human tissue (Lombardo et al., 1996 Beck et al., 1997 Vreugdenhil et al., 1998 Straub et al., 2000). 

Spider Peptides High molecular weight proteins Polyamines Selective action on voltage-dependent sodium, potassium and calcium channels Induction of neurotransmitter release Antagonists of ionotropic glutamate receptors Enzyme-linked immunosorbent assay 10-20 ngmr ... 

O Leary ME, Hancox JC. Role of voltagegated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias. Br J Clin Pharmacol 2010 69(5) 427-42. 

Targets for toxins can be considered to exist at various levels. Toxins may evolve which subdue prey by either blocking the systems responsible for locomotion, circulation, or for central coordination, in the potential victim. In order to disable these systems, advantage is often taken of the fact that their physiology depends upon specific transmembrane channels such as those for sodium, potassium, and calcium ions. 

Sour and salty. Within the membrane of the taste cell are ion channels which control the movement of ions, such as sodium, potassium and calcium, into and out of the cell. Sour taste sensations are in part due to the effect of hydrogen ions however, some taste is also a function of the hydrophobicity of the organic acid, such as citric acid (18). Acids can produce a decrease in potassium ion conductance (depolarization) in the membrane. 

Ion channels are transmembrane proteins that span the cell membrane and are formed from one or more protein subunits. The channels are shaped like tunnels, which form pores through the plasma membrane. The pores have gates that open and close to allow ions to diffuse down their chemical gradient and move in or out of a cell. Ion channels are specific for certain types (and combinations of types) of ions, such as chloride, sodium, potassium, and calcium. 

Ion channels are ubiquitous and undoubtedly occur in the lipid bilayer of all cell membranes. They have many functions and some are critical to cellular activity. These include the generation of cellular energy, the production of electric signals in the nervous system, and a variety of signal-transduction processes. The inorganic ions involved in this signaling include sodium, potassium, and calcium. Each... 

Antiarrhythmics act by blocking the membrane sodium, potassium and calcium ion channels, but no agent has an exclusive action on a given type of channel. Additive effects may occur from drugs that affect different channels. 

Local anesthetics have a wide range of effects. They inhibit sodium, potassium, and calcium ion channels, alpha-adrenoceptors, and phosphatidylinositol signalling. They also cause dysrhythmias when injected directly into the brain. Local anesthetics are also mitochondrial poisons and impair oxidative phosphorylation. 

Current research is focusing on excitatory and inhibitory neurotransmitters, secondary messengers, neuroendocrines, and neuropeptides. Areas of receptor research include subtypes of central and peripheral GABA receptors, and dopamine receptor subtypes. Cell membrane properties and ion channels for sodium potassium and calcium are also being investigated. 

Phenytoin is a hydantoin derivative like dantrolene and the oldest non-sedative anticonvulsant drug known. It alters sodium, potassium and calcium conductance across cell membranes thereby altering membrane potentials and amino acid and neurotransmitter concentrations (i.e. norepinephrine (noradrenaline), acetylcholine and GABA). Its major mode of action appears to be the blockade of sodium channels and e inhibition of the generation of repetitive action potentials (membrane stabilization) (see Chs 9 and 12). 

Chloride is mostly described in relation to hydrogen, sodium, potassium, and calcium, except when deviations are well described specifically for Cl in biological systems as a result of deficiency or excess availability. In addition, dysfunctions of CD transport or CD channels are of clinical relevance and have indeed been the subject of intensive research. One principle of CD-mediated effects is a change in osmotic condition, cell volume, and excitability and in acid-base balance in biological systems. In this way, CD is essentially linked to water distribution and electrolyte turnover. 

Lamprey CNS neurons The model of Brodin et al. [1991 ] consisted of voltage-gated sodium, potassium and calcium currents, a calcium-activated potassium current, and an NMDA receptor channel. The voltage-dependent block by magnesium of the NMDA was also modeled in this paper. Two compartments were used to model calcium concentration changes inside the cells. 

A detailed model of the slow processes in principal cells of the cortical collecting tubule of the mammalian kidney was buQt by Tang and Othmer [1996] and includes sodium, potassium, and chloride channels a sodium-potassium pump a calcium pump a sodium-potassium-chloride cotransporter and a sodium-calcium exchanger. 

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