Calcium channels other channel types

Nifedipine (a dihydropyridine) Block of vascular L-type calcium channels > cardiac channels Like verapamil and diltiazem less cardiac effect Prophylaxis of angina, hypertension Oral, duration 4-6 h Toxicity Excessive hypotension Interactions Additive with other vasodilators... 

Apart from HCN channels, genistein (42) also acted on other types of channels present in cardiac cells. Chiang et al. [306] examined the impact of this isoflavone on the L-type calcium and cAMP- dependent chloride currents in guinea pig ventricular myocytes. Using the voltage-clamp technique they found that genistein (42) reversibly inhibited L-type calcium currents in a dose-dependent manner. Surprisingly daidzein (40), which was ineffective with respect to many other channel types, also decreased L-type calcium currents in myocytes. Opposite to calcium currents, the cAMP-dependent... 

Succinimides. Ethosuximide [77-67-8] C2H22NO2 (41) and the related succinknide, methsuximide [77-41-8] C22H23NO2 (42) are used in absence seizure treatment. Like the other anticonvulsants discussed, the mechanism of action of the succinirnides is unclear. Effects on T-type calcium channels and -ATPase activity have been reported (20). Ethosuximide has significant CNS and gastrointestinal (GI) side effect HabiUties (13). 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

Coetzee and Opie (1988, 1992) have suggested that the cellular calcium overload induced by oxidant stress is mediated by an increase in calcium influx through the L-type calcium channel. However, a number of other studies, using different radical-generating systems, experimental conditions and species, have described no significant effects on the calcium channel over the period of exposure necessary to induce cellular calcium overload (Bhatnagar etal., 1990 Shattock etal., 1990 Beresewicz... 

A series of 2-amino-3/4-dihydro quinazolines have been extensively explored as selective T-type calcium channel antagonists. A recent disclosure included KYS05090 (9) with an IC50 of 41 nM on the Cav3.1 subtype of the T-type channel and 120-fold selectivity versus the N-type calcium channel Cav2.2 [55]. A pharmacophore model was recently published based on this and related structures [56], but no other selectivity or in vivo activity have been disclosed since the original report. 

Increases in the concentration of calcium in the cytosol provides a signal that can initiate muscle contraction, vision, and other signaling pathways. The response depends on the cell type. In muscle, a transient rise in the cytosolic calcium levels (from opening calcium channels in the sarcoplasmic reticulum) causes contraction. This signaling in contraction is a direct consequence of electrical activation of the voltage-gated channel. 

Channels associated with capacitative calcium ion entry have been characterized electrophysiologically. In leukocytes, the current associated with the depletion of intracellular Ca2+ stores is highly Ca2+-selective and, on the basis of noise analysis, is believed to involve minute single channels [16] (see Ch. 6). This is the calcium release-activated calcium current (ICrac)- In other cell types, currents with significantly different properties have been identified, including in some instances store-operated nonse-lective cation channels. These marked electrophysiological distinctions may be indicative of distinct channel types mediating capacitative calcium ion entry in different cell types. 

Obviously, the effects of tamoxifen and derivatives and of raloxifene on L-type calcium channels from aortic and other blood vessels would reduce vascular smooth muscle contractility. This action, in synergy with the aforementioned effect on BK channels, would reduce blood peripheral resistance and blood pressure, which may partially account for the reduction in cardiovascular risk (Da Costa et al. 2004 Trump et al. 1992) (Fig. 4.1). 

Other target sites for certain pyrethroids include the voltage-gated calcium and chloride channels. Of particular interest is the increased effect of Type II pyrethroids on certain phosphoforms of the N-type Cav2.2 calcium channel following post-translational modification and its relationship to enhanced neurotransmitter release seen in vivo. 

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