Current Molecular Pharmacology - Volume 8, Issue 1, 2015

Voltage-gated calcium channels are not only mediators of cell signalling events, but also are recipients of signalling inputs from G protein coupled receptors (GPCRs) and their associated second messenger pathways. The coupling of GPCRs to calcium channels is optimized through the formation of receptor-channel complexes. In addition, this provides a mechanism for receptorchannel co-trafficking to and from the pla Read More

Intracellular calcium transients generated by activation of voltage-gated calcium (CaV) channels generate local signals, which initiate physiological processes such as secretion, synaptic transmission, and excitation-contraction coupling. Regulation of calcium entry through CaV channels is crucial for control of these physiological processes. In this article, I review experimental results that have emerged over several years showing Read More

Voltage-gated calcium ion channels are essential for numerous biological functions of excitable cells and there is wide spread appreciation of their importance as drug targets in the treatment of many disorders including those of cardiovascular and nervous systems. Each Cacna1 gene has the potential to generate a number of structurally, functionally, and in some cases pharmacologically unique CaVα1 subunits through altern Read More

The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by increasing the membrane permeability to Ca2+, a major signal for cardiac muscle contraction, regulation of vascular tone and CREB-dependent transcriptional activation. CACNB2 is one of the four homologous genes coding for the auxiliary Cavβ subunits, which are important modulators of the Ca2+ channel activity. Five serious me Read More

Ca2+ influx via L-type Ca2+ channel (L-VDCC; CaV1.2) is required for cardiac and smooth muscle contraction. These channels are located in the plasma membrane and along the T-tubules (in cardiomyocytes), along with various scaffold and trafficking proteins. CaV1.2 is modulated by different hormones and transmitters and was implicated in a variety of cardiovascular pathologies, many of which also involve protein ki Read More

The major function of the voltage-gated calcium channels is to provide the Ca2+ flux into the cell. L-type voltage-gated calcium channels (Cav1) serve as voltage sensors that couple membrane depolarization to many intracellular processes. Electrical activity in excitable cells affects gene expression through signaling pathways involved in the excitation-transcription (E-T) coupling. E-T coupling starts with activation of the Ca Read More

The cardiac L-type Ca2+ channel plays a key role in cardiac excitation-contraction coupling, action potential duration, and gene expression. Abnormalities in CaV1.2 function, including increased long-opening-mode gating and blunted adrenergic responsiveness, are associated with heart failure and hypertrophy. The increased activation of CaV1.2, in turn, triggers Ca2+ -responsive signaling pathways, which contribute to t Read More

Voltage-gated calcium (CaV) channels conduct Ca2+ ions into cells in response to depolarization and thereby contribute to regulate diverse biological events in a wide variety of tissues including nerves, glands and muscles. They are responsible for initiation of excitation-contraction and excitation-secretion coupling, and are involved in the regulation of protein phosphorylation and gene transcription, among many other i Read More

Here we review the contribution of the various subtypes of voltage-activated calcium channels (VACCs) to the regulation of catecholamine release from chromaffin cells (CCs) at early life. Patch-clamp recording of inward currents through VACCs has revealed the expression of highthreshold VACCs (high-VACCs) of the L, N, and PQ subtypes in rat embryo CCs and ovine embryo CCs. Low-threshold VACC (low-VACC) currents (T-t Read More

Calcium agonists such as FPL 64174 increase macroscopic calcium channel currents and induce substantial changes in current kinetics. Their molecular mechanism of action is currently unknown. Here we propose a technique enabling the estimation of FPL 64174 effects on rate constants of the voltage sensing machinery and pore transitions from macroscopic CaV1.2 current kinetics making use of a hybrid stochastic-dete Read More

Alterations in dendritic spine morphology and postsynaptic structure are a hallmark of neurological disorders. Particularly spine pruning of striatal medium spiny neurons and aberrant rewiring of corticostriatal synapses have been associated with the pathology of Parkinson’s disease and LDOPA induced dyskinesia, respectively. Owing to its low activation threshold the neuronal L-type calcium channel CaV1.3 is particularly critical i Read More

During the past decades, an increasing number of ion channel and transporter types have been identified acting together to produce cardiac and neuronal pacemaker action potentials. The basis of pacemaker activity was understood in more detail by using single-microelectrode recordings on cells isolated from pacemaker regions. Meanwhile, this powerful technique was complemented by computer modeling and recombinant Read More