Voltage calcium channels

Diltiazem inhibits calcium influx via voltage-operated channels and therefore decreases intracellular calcium ion. This decreases smooth muscle tone. Diltiazem dilates both large and small arteries and also inhibits a-adrenoceptor activated calcium influx. It differs from verapamil and nifedipine by its use dependence. In order for the blockade to occur, the channels must be in the activated state. Diltiazem has no significant affinity for calmodulin. The side effects are headache, edema, and dizziness. 

Catterall WA, Perez-Reyes E, Snutch TP et al (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57 411-425... 

Furthermore, PKCe is required for nerve growth factor-induced activation of mitogen-activated protein kinases and neurite outgrowth by ethanol. It is also required for ethanol-induced increases in N-type voltage-gated calcium channels in PC 12 neural cells. 

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]. 

High voltage-activated (HVA) calcium channels Low voltage-activated (LVA) calcium channels... 

Voltage-dependent Ca2+ channels are a family of multi-subunit complexes of five proteins responding to membrane depolarisation with channel opening allowing the influx of calcium into a cell. Voltage-dependent calcium channels are subdivided into three subfamilies the HVA DHP-sensitive L-type calcium channels, the HVA DHP-insensitive calcium channels and the LVA T-type calcium channels [2]. 

HVA calcium channels are biochemically hetero-oligomeric complexes of five proteins encoded by four gene families (Fig. 1) The ax subunits of 190-250 kDa contain the voltage-sensor, the selectivity filter, the ion-conducting pore, the binding sites for most calcium... 

Voltage-dependent Ca2 Channels. Figure 1 Structure, identity and blockers of calcium channel subunits. 

Voltage-dependent Ca2+ Channels. Figure 2 Subunit composition of a HVA calcium channel. The selectivity filter of the channel is created by four glutamates (E). 

More recent analysis of tissue specific gene deletions showed that the Cav1.2 channel is involved in a wide variety of function including hippocampal learning, insulin secretion, intestine and bladder motility. Further analysis will be required to unravel the functional significance of voltage-dependent calcium channels for specific cellular functions. 

Hofmann F, Lacinova L, Klugbauer N (1999) Voltage-dependent calcium channels from structure to function. Rev Physiol Biochem Pharmacol 139 33-87... 

Lacinova L, Klugbauer N, Hofmann F (2000) Low voltage activated calcium channels from genes to function. Gen Physiol Biophys 19 121-136... 

Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83 117-161... 

Carmignoto G, Pasti L, Pozzan T (1998) On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ. J Neurosci 18 4637-4645 Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48 16 2... 

Brown, DA (2000) The acid test for resting potassium channels. Curr. Biol. 10 R456-R459. Dolphin, AC (1998) Mechanisms of modulation of voltage-dependent calcium channels by G proteins. J. Physiol. 506 3-11. 

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. 

L-type calcium channels (voltage-gated calcium channels L-subtype) Similarity to Diltiazem and a second ligand. ZINC db ( 50 K commercially available subset screened but most filtered to achieve desired PK profile using VolSurf). SHOP similarity, and feature-presence filtering down to 36 compounds 7 hits 18 tested, active in a vasorelaxant assay and some had novel structures. [67]... 

Ikeda, S. R. and Dunlap, K., Voltage-dependent modulation of N-type calcium channels role of G-protein subunits, Adv. Second Messenger Phosphoprotein Res., 33, 131-151, 1999. 

---