Calcium channel voltage-sensitive

Stimulation of mAChRs also results in the activation or inhibition of a large number of ion channels [5]. For example, stimulation of Mi receptors leads to the suppression of the so-called M current, a voltage-dependent Recurrent found in various neuronal tissues. M2 receptors, on the other hand, mediate the opening of cardiac Ikcacii) channels, and both M2 and M4 receptors are linked to the inhibition of voltage-sensitive calcium channels [5]. 

Although there is no evidence that the neuronal degeneration of AzD results, as in cardiovascular ischaemia, from the excitotoxicity of increased intracellular Ca +, some calcium channel blockers have been tried in AzD. They have had little effect but surprisingly a pyrrolidone derivative nefiracetam, which opens L-type voltage-sensitive calcium channels (VSCCs) reduces both scopolamine- and )S-amyloid-induced impairments of learning and memory in rats (Yamada et al. 1999). This effect can be overcome by VSCC antagonists, but nefiracetam has not been tried in humans. 

Neurotransmitter release induced by potassium-dependent depolarization is a physiologically relevant way to investigate pyrethroid effects on calcium-dependent neurotransmitter release since this process is independent of voltage-sensitive sodium channels [71]. Furthermore, potassium-stimulated calcium influx and subsequent neurotransmitter release by synaptosomes is blocked by a variety of voltage-sensitive calcium channel antagonists but not by TTX [4, 71, 72]. 

Shafer TJ, Meyer DA (2004) Effects of pyrethroids on voltage-sensitive calcium channels a critical evaluation of strengths, weaknesses, data needs, and relationship to assessment of cumulative neurotoxicity. Toxicol Appl Pharmacol 196 303-318... 

Symington SB, Clark JM (2005) Action of deltamethrin on N-type (Cav2.2) voltage-sensitive calcium channels in rat brain. Pestic Biochem Physiol 82 1-15... 

Mutanguha EM, Valentine ZH, Symington SB (2010) Pyrethroid inhibition of a human T-type voltage-sensitive calcium channel is structural specific and concentration -dependent. 49th Annual Society of Toxicology, Salt Lake City, UT... 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

Bowersox, S.S., Gadbois, Th., Singh, T., Pettus, M., Wang, Y.-X., Luther, R.R. Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX - 111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain, J. Pharmacol. Exper. Ther. 1996, 279, 1243-1249. 

Brose, W.G., Gutlove, D.P., Luther, R.R., Bowersox, S.S., McGuire, D. Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain, Clin. J. Pain, 1997, 13, 256-259. 

Malmberg, A.B. and Yaksh, T.L. Voltage-sensitive calcium channels in spinal nociceptive processing Blockade of N- and P-type channels inhibits formalin-induced nociception, J. Neurosci. 1994, 14, 4882-4890. 

Wang, Y-X., Gao, D., Pettus, M., Phillips, C., Bowersox, S.S. Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats, Pain 2000, 84, 271-281. 

Calcium channels are a third major group of cation-selective channels.514 As pointed out in Box 6-D, calcium ions are involved in a very wide range of signaling functions. These are discussed in several places in this book. Several of these functions depend upon voltage-gated Ca2+ channels. Muscle is rich in L-type or DHP-sensitive channels (Box 6-D) which play a role in transmission of nerve impulses to muscles by allowing rapid flow of calcium ions into cells from outside.515... 

Rossie, S. (1999) Regulation of voltage-sensitive sodium and calcium channels by phosphorylation. Advances in Second Messenger and Phosphorylation Research 33, 23 18. 

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