BACKGROUND The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. METHODS AND RESULTS We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The sin...

The molecular heterogeneity of voltage-gated calcium channels is mirrored by extensive biophysical diversity. Subtype-selective antagonists have been used to place different kinds of calcium channels in functional categories. Dihydropyridine (DHP) antagonists have been used, for example, to implicate L-type calcium channels in the induction of NMDA receptor-independent forms of synaptic plastic...

The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium chann...

Using the whole-cell clamp technique, we show that L-type calcium channels are activated in early sea urchin blastomeres during M-phase and subsequently inactivated in S-phase. This cyclical channel behaviour occurs in the absence of the nucleus suggesting cytoplasmic regulation independent of the centrosome cycle. Puromycin at 100-400 μM does not prevent inactivation of the current showing tha...

Voltage-dependent L-type calcium channels were induced in highly purified, cultured, cortical astrocytes by exposure to substances known to increase their intracellular cAMP: 8-bromo-cAMP, forskolin, isoproterenol, and vasoactive intestinal peptide. In untreated control cultures, L-type calcium currents were entirely absent. The induction of this calcium current was specific to cortical astrocy...

nimodipine, an l-type calcium channel blocker, can induce analgesia. however, it is not clear that this analgesic effect is at the level of spinal or supraspinal pain pathway. in addition, it has been reported that the analgesic effect of nifedipine, another l-type calcium channel blocker is related to the hpa axis, but there is no report indicating the role of this axis in the analgesic effect...

Hypothalamic AMP-activated protein kinase (AMPK) and orexins/hypocretins are both involved in the control of feeding behavior, but little is known about the interaction between these two signaling systems. Here, we demonstrated that orexin-A elicited significant activation of AMPK in the arcuate nucleus (ARC) of the hypothalamus by elevating cytosolic free Ca²⁺ involving extracellular calcium i...

Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are ...

Lamprey spinal cord neurons possess N-, L-, and P/Q-type high-voltage-activated (HVA) calcium channels. We have analyzed the role of the different HVA calcium channels subtypes in the overall functioning of the spinal locomotor network by monitoring the influence of their specific agonists and antagonists on synaptic transmission and on N-methyl-D-aspartate (NMDA)-elicited fictive locomotion. T...