State-dependent calcium channel

Narita, M., Nakajima, M., Miyoshi, K., Narita, M., Nagumo, Y., Miyatake, M., Yajima, Y., Yanagida, K., Yamazaki, M., and Suzuki, T. (2007). Role of spinal voltage-dependent calcium channel alpha 2 delta-1 subunit in the expression of a neuropathic pain-like state in mice. Life Sci. 80, 2015-2024. 

Calcium homeostasis is also affected by an overload in peroxides. In some instances, this may be due to activation of so-called calcium channels. In the presence of extracellular calcium, exposure of smooth muscle cells to 0.3 mM H2O2 was shown to induce a rapid increase in intracellular calcium concentration, followed by a decrease to a new constant level approximately twice higher than the initial one [140]. Subsequent treatment of the cells with Ca2+-channel blockers, with disulfide-reducing agents or with antioxidants such as trolox, prevented the stabilization of intracellular calcium at the high steady-state concentration. These results suggest that an increased disulfide/thiol ratio activates voltage-dependent calcium channels of the outer cell membrane. 

As with the effects of oxidant stress on the calcium channel, part of the change in the steady-state background current could also be attributed to an indirect effect secondary to the elevation of intracellular calcium (Matsuura and Shattock, 1991b). However, oxidant stress also exerted a direct effect on the inward rectifying potassium current (7ki). The combination of an inhibition of 7ki and the activation of a calcium-dependent current are likely to contribute to the prolongation of the action potential duration and the increased susceptibility... 

Autonomic receptors further regulate calcium influx through the sarcolemma (Fig. 15.1). (3-Adrenergic stimulation results in the association of a catalytic subunit of a G protein coupled to the (3-receptor. This stimulates the enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (cAMP). Increasing cAMP production results in a cAMP-dependent phosphorylation of the L-type calcium channel and a subsequent increase in the probability of the open state of the channel. This translates to an increase in transsarcolemmal calcium influx during phase 2 (the plateau phase) of the cardiac muscle action potential. The effects of transient increases in intracellular levels of cAMP are tightly con-... 

Unlike genistein (42), quercetin (29) [308,309] and myricetin (31) [310] enhanced the calcium current carried by L-type calcium channels of the myocytes from rat tail artery. The character of voltage-, concentration-, and frequency-dependent calcium current changes induced by myricetin (31) [310] allowed the conclusion that this flavonoid exerted its effect on L-type calcium channels by binding preferentially to the channels in the inactivated state. Quercetin stimulated L-type calcium channels in rat pituitary GH3 cells in a dose-dependent manner [309]. The EC50 value was about 7 xM, and many facts suggested direct interaction between ion channels and flavonoid. In NG 108-15 neuronal cells quercetin (29) caused inhibition of TTX-sensitive sodium current. 

The specific Ca channel antagoni.sts verapamil, nifedipine, and diltiazem interact at specific sites on the calcium channel protein. These blockers do not occlude the channel physically but bind to sites in the channel, as they can promote both channel activation and antagonism. AITiniiy fix binding sites on the channel varies, depending un the status of the channel. The channel can exist in either an open (0. re.sting (R). or inactivated (I) state, and the equilibrium lx-, tween them is determined by stimulus frequency and mem-... 

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