Calcium cycling figures prominently in excitation-contraction coupling and in various signaling cascades involved in the development of left ventricular hypertrophy. We hypothesized that genetic suppression of the L-type calcium channel accessory beta-subunit would modulate calcium current and suppress cardiac hypertrophy. A short hairpin RNA template sequence capable of mediating the knockdown...

Voltage-dependent calcium channels regulate many aspects of neuronal biology, including synaptic transmission. In addition to their alpha1 subunit, which encodes the essential voltage gate and selective pore, calcium channels also contain auxiliary alpha2delta, beta, and gamma subunits. Despite progress in understanding the biophysical properties of calcium channels, the in vivo functions of th...

The pore-forming subunits of canonical voltage-gated sodium and calcium channels are encoded by four repeated domains of six-transmembrane (6TM) segments. We expressed and characterized a bacterial ion channel (NaChBac) from Bacillus halodurans that is encoded by one 6TM segment. The sequence, especially in the pore region, is similar to that of voltage-gated calcium channels. The expressed cha...

The agents commonly called the calcium channel blockers comprise an increasing number of agents, including the prototypical verapamil (Calan, Isoptin), nifedipine (Adalat, Procardia), and diltiazem (Cardizem). These agents are a chemically and pharmacologically heterogeneous group of synthetic drugs, but they possess the common property of selectively antagonizing Ca movements that underlie the...

T he concept of proarrhythmia, the realization that antiarrhythmic drugs can occasionally drastically aggravate the very problem for which they were prescribed, is now widely appreciated and has undoubtedly lead to an overall improvement in the use of these drugs. Proarrhythmia is a particularly dangerous type of side effect: It is unpredictable, may easily escape detection, and can turn a beni...

1522-8401/$ see fro doi:10.1016/j.cpem.2 Department of Eme Children’s Hospit RI 02903, USA. Reprint requests and Department of E Children’s Hospit RI 02903, USA. Calcium-channel blockers (CCB) were first developed in the 1960s. Since then, the list of formulations and variety of uses has increased significantly. Unfortunately, toxic exposures to CCBs have also increased since their debut. This ...

Glutamate release from rod photoreceptors is dependent on a sustained calcium influx through L-type calcium channels. Missense mutations in the CACNA1F gene in patients with incomplete X-linked congenital stationary night blindness implicate the Ca(v)1.4 calcium channel subtype. Here, we describe the functional and pharmacological properties of transiently expressed human Ca(v)1.4 calcium chann...

The effects of auxiliary calcium channel subunits on the expression and functional properties of high-voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel beta and alpha(2)-delta sub...

We have investigated the effects of etomidate 4.4 mumol litre-1, 1.0 mg litre-1 and 27.4 mumol litre-1, 6.25 mg litre-1 on whole-cell and single L-type calcium channel currents in myocytes from guineapig ventricles. For whole-cell recordings, the cells were voltage-clamped and step depolarizations were applied from holding potential of -40 mV to various potentials to elicit L-type calcium curre...

We have previously presented evidence that electrical activity and increased cytosolic calcium reduce the density of sarcolemmal tetrodotoxin (TTX)-sensitive sodium channels in cultured rat muscle cells (Sherman, S. J., and W. A. Catterall (1984) Proc. Natl. Acad. Sci. U. S. A. 81: 262-266). We show here that growth of cells in ryanodine has a biphasic effect on sodium channel number. At low co...