Voltage-dependent Ca2+ Channels

Voltage-dependent Na+ Channels Voltage-dependent Ca2+ Channels (3-Adrenergic System Cardiac Glycosides... 

Ionotropic Glutamate Receptors Voltage-dependent Ca2+ Channels Voltage-gated K+ Channels... 

An oligomeric protein that spans a cell membrane forming a regulated pore through which Ca2+ can pass. Ca2+ channels differ considerably in their selectivity for Ca2+ over other cations For example DP3R are poorly selective, voltage-dependent Ca2+ channels are vety selective. 

Inwardly Rectifying K+ Channels ATP-dependent K+ Channels Voltage-dependent Ca2+ Channels Ryanodine Receptor Voltage-dependent Na2+ Channels... 

Voltage-dependent Ca2+ Channels Ca2+ Channel Blockers Ryanodine Receptor... 

Episodic ataxia (EA) is an autosomal dominant disorder that brief episodes of ataxia can be triggered by physical or emotional stress. The symptom can occur several times during the day, last for seconds to minutes, and be associated with dysarthria and motor neuron activity, which causes muscle rippling (myokymia) between and during attacks. It is caused by a mutation in a neuronal voltage dependent Ca2+ channel. 

Voltage-dependent Ca2+ channels that are activated at a membrane potential around -30 mV with a maximal inward current around OmV. 

Voltage-dependent Ca2+ channels are a family of multi-subunit complexes of five proteins responding to membrane depolarisation with channel opening allowing the influx of calcium into a cell. Voltage-dependent calcium channels are subdivided into three subfamilies the HVA DHP-sensitive L-type calcium channels, the HVA DHP-insensitive calcium channels and the LVA T-type calcium channels [2]. 

Voltage-dependent Ca2 Channels. Figure 1 Structure, identity and blockers of calcium channel subunits. 

Voltage-dependent Ca2+ Channels. Figure 2 Subunit composition of a HVA calcium channel. The selectivity filter of the channel is created by four glutamates (E). 

Muth JN, Varadi G, Schwartz A (2001) Use of transgenic mice to study voltage-dependent Ca2+ channels. Trends Pharmacol Sci 22 526-532... 

CFTR potentiator (F508del-CFTR Ka= 0.11 pM, G551D-CFTR Ka= 1.2 pM) with 250-fold selectivity over the L-type voltage-dependent Ca2+ channel [52,53],... 

Ionized calcium (Ca2+) is the most common signal transduction element in cells [66], Excitable cells, like neurons, contain voltage-dependent Ca2+ channels, which enable these cells to drastically increase cytosolic calcium levels. Rapid fluctuations in presynaptic... 

Ca2+ can enter cells via voltage- or ligand-dependent channels and by capacitative entry. These three fundamental mechanisms of regulated calcium ion entry across the plasma membrane involve, respectively, voltage-dependent Ca2+ channels, ligand-gated Ca2+ channels and capacitative Ca2+ entry associated with phospholipase C-coupled receptors. 

There are at least five different types of voltage-dependent Ca2+ channel molecules, differing in their gating kinetics, modes of Ca2+-inactivation and Ca2+-iregulation, and sensitivity to specific marine toxins [13] (see Ch. 6). The distinctions between the types of channel are of considerable interest because the different subtypes are believed to subserve different cellular functions. For example, the control of neurotransmitter release in peripheral sympathetic neurons appears to be under the predominant control of N-type calcium channels. 

Recent work using confocal microscopy has found localized increases of [Ca2+]j named Ca2+ sparks which are due to the release of Ca2+ from one or a small number of RyRs (Jaggar et al 2000). These localized releases of Ca2+ activate Ca2+-dependent channels in the surface membrane (Perez et al 2001). Activation of the Ca2+-activated K+ current will hyperpolarize the membrane potential (Herrera et al 2001) and thereby decrease Ca2+ entry into the cell on voltage-dependent Ca2+ channels. This provides a mechanism whereby Ca2+ release from the SR can decrease contraction. It is therefore important, in different smooth muscles, to consider to what extent SR Ca2+ release activates rather than decreases contraction. It is, of course, possible that, in the same smooth muscle, SR release may sometimes directly activate contraction and, at other times, decrease it by activating K+ channels. 

Nelson There is an emerging theme of calmodulin being tightly bound to almost all its targets. For example, the SK channel is gated by calmodulin, and is extremely tightly bound. Another example is the voltage-dependent Ca2+ channel, where calmodulin is also bound and involved in inactivation. 

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