Voltage-operated calcium channel

When the action potential reaches the synaptic bouton, depolarisation triggers the opening of voltage-operated calcium channels in the membrane (Figure 2.5). The concentration gradient for Ca2+ favours the passive movement of this ion into the neuron. The subsequent rise in cytoplasmic Ca2+ ion concentration stimulates the release of neurotransmitter into the synaptic cleft, which diffuses across this narrow gap and binds to receptors located on the postsynaptic neuronal membrane (Figure 2.5). 

Figure 2.5. The synapse. GPCR = guanine nucleotide-binding protein-coupled receptor, LGICR = ligand-gated ion channel receptor, SB = synaptic bouton, T = neurotransmitter, YOC = voltage-operated ion channel protein, YOCC = voltage-operated calcium channel protein, Ast = astrocyte, AA = axoaxonal synapse, ASD = axosomatic or axodendritic synapse. GPCR 1 = receptor protein, 2 = G-protein, 3 = enzyme, 4 = ion channel protein.

Activation of opioid receptors produces effects that are primarily inhibitory. Opioid-mediated inhibition of adenylyl cyclase decreases cAMP production. Opioids also close A/-type voltage-operated calcium channels and... 

Increased Ca2+ influx through voltage-operated calcium channels (VOCCs) is... 

Barone F., Aguanno S., D Alessio A., and D Agostino A. 2004 Sertoli cell modulates MAA-induced apoptosis of germ cells throughout voltage-operated calcium channels. Faseb J 18, 353-354. 

Bobich, J. A., Zheng, Q., and Campbell, A. (2004). Incubation of nerve endings with a physiological concentration of Abetal—42 activates CaV2.2(N-Type)-voltage operated calcium channels and acutely increases glutamate and noradrenaline release. J Alzheimers Dis 6, 243—255. 

Zahanich I, Graf EM, Heubach JF, Hempel U, Boxberger S, Ravens U. 2005. Molecular and functional expression of voltage-operated calcium channels during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res 20 1637-46. 

Subsequently, several studies have provided more detailed information on domoic acid action as an excitotoxin. The presynaptic action of domoic acid to induce glutamate release was extended to include other excitatoiy and inhibitoiy neurotransmitters and linked to the entiy of calcium through voltage operated calcium channels, suggesting that domoic acid toxicity may involve multiple transmitters (Brown and Nijjar 1995 Duran et al. 1995a Malva et al. 1996). Domoic acid effects on intracellular calcium were next characterized by FURA-2 imaging of the hilar region of individual... 

It has been proposed that KCAs, such as cromakalim (I), induce their relaxations by opening K tp, the channels closed by ATP, and hyperpolarising the cell membrane. This causes closure of voltage-operated calcium channels and may also affect intracellular calcium stores, the overall result being a relaxation of smooth muscle tone. Other reviews [3,11, 75-79] provide more detailed explanations of the mechanisms involved in KCA-induced relaxations. 

Figure 7.1. Diagrammatic representation of cellular Ca2 movements. Calcium ions (Ca2 ) may cross the sarcolemma by the following routes (7) voltage-operated calcium channels Q) receptor-operated calcium channels ( ) fast sodium channels (7) Ca2 -A TPase pump (J) Na -Ca2 exchange and Ca2 + leak pathways. Inside the cell, Ca2 may be taken up into and released from mitochondria (MIT) and sarcoplasmic reticulum (SR) (8). Ca2 also binds to the intracellular proteins, calmodulin and troponin C. REC represents a specific membrane receptor site.

Wijetunge S, Lymn JS, Hughes AD. Effects of protein tyrosine kinase inhibitors on voltage-operated calcium channel currents in vascular smooth muscle cells and ppOO kinase activity. Br J Pharmacol 2000 129 1347-1354. 

Valentijn, K. et al., Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(-t)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices. Brain Res Mol Brain Res 14, 221, 1992. 

Spasmolytic Effect. Isojuripidine, an alkamine of the 3-aminospirostan type, showed a spasmolytic effect in guinea-pig ileum due to a partially blockade of calcium influx through voltage-operated calcium channels (De Cassia Meneses Oliveira et al. 2006). 

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