Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca(2+) channels. In heart cells, a tight coupling between the gating of single L-type Ca(2+) channels and ryanodine receptors (RYRs) underlies calcium release. Here we demonstrate that L-type Ca(2+) channels activate RYRs to pro...

Hydrogen sulfide (H(2)S) is a novel gasotransmitter that inhibits L-type calcium currents (I (Ca, L)). However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H(2)S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in r...

the protective effect of a l-type calcium channel blocker, nimodipine, on cell injury induced by oxygen-glucose deprivation (ogd) in pc12 cells was investigated. pc12 cells were exposed to in-vitro oxygen-glucose deprivation (30 minutes and 60 minutes respectively) in the presence or absence of nimodipine (10mm/l) in three different time schedules (pre-24h, pre-3h and concurrently). cellular vi...

The calcium channels play a key role in controlling many physiological processes in the body. Voltage dependent calcium channels have been extensively characterized in terms of their electrophysiological and pharmacological properties. The L-type voltage-dependent calcium channel is composed of several subunits, from which the alpha 1 subunit is the most important. Recent interest has been focu...

We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type cal...

Ca(2+) entry is delicately controlled by inactivation of L-type calcium channel (LTCC) composed of the pore-forming subunit alpha1C and the auxiliary subunits beta1 and alpha2delta. Calmodulin is the key protein that interacts with the COOH-terminal motifs of alpha1C, leading to the fine control of LTCC inactivation. In this study we show evidence that a hyperpolarization-activated cyclic nucle...

The goal of these studies was to determine whether different calcium channel antagonists affect glucose transport in a neuronal cell line. Rat pheochromocytoma (PC-12) cells were treated with L-, T-, and N-type calcium channel antagonists before measurement of accumulation of 2-[(3)H]deoxyglucose (2-[(3)H]DG). The L-type channel antagonists nimodipine, nifedipine, verapamil, and diltiazem all i...