Voltage-gated Ca2 channels

Ca2+ is a major second messenger in eukaryote cells, the cytosolic free concentration of Ca2+ being elevated in response to depolarization and to many hormones and NTs. Intracellular and PM voltage-gated Ca2+ channels are accordingly involved in Ca2+-mediated signalling. 

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Voltage-gated Ca2+ channels are Ca2+-selective pores in the plasma membrane of electrically excitable cells, such as neurons, muscle cells, (neuro) endocrine cells, and sensory cells. They open in response to membrane depolarization (e.g., an action potential) and permit the influx of Ca2+ along its electrochemical gradient into the cytoplasm. 

Ca2+ Channel Blockers. Figure 1 Most voltage-gated Ca2+ channels exist as a hetero-oligomeric complex of several subunits, a 1 subunits form the Ca2+-selective ion pore and contain the voltage-sensors of the channel. 

G0 was isolated as an other PTx-ribosylated G-protein which co-purifies with G, but which does not inhibit adenylate cyclase. There are two main isoforms (G0l and Go2), with additional splice-variants. G0 is particularly abundant in the nervous system, comprising up to 1% of membrane proteins. Its main function is to reduce the opening probability of those voltage-gated Ca2+ channels (N- and P/Q-type) involved in neurotransmitter release. Hence, it is largely responsible for the widespread auto-inhibition of transmitter secretion by presynaptic receptors and this effect is mediated through released py subunits. 

Voltage-gated Ca2+ channels Mediate Ca2+ influx for neurotransmitter release at the active zone. 

Thus the SR may alter membrane potential via KCa and ClCa, and may thereby affect voltage-gated Ca2+ channel entry and force. We have recently examined the role of the SR in the guinea-pig ureter by emptying it of releasable Ca2+ and determining the effects. 

In muscle cells and neurones a second mechanism exists for the release of intracellular Ca2-i-, involving ryanodine receptors in the endoplas mic reticulum (ER) membrane. This pathway is activated by an action potential opening a plasma membrane voltage-gated Ca2+ channel, allowing a small influx of extracellular Ca2+. Binding of Ca2+ to the ryanodine receptor triggers a massive release of Ca2+ from the ER stores. 

Arrival of the nerve impulse at a nerve terminal leads to the opening of voltage-gated Ca2+ channels and rapid influx of Ca2+. The increase in Ca2+ concentration at the active zone from a basal level of 100 nM to more than 200 pM results in an appropriate neurotransmitter release within 200 ps (Barrett and Stevens, 1972 Linas et al., 1981 1992 Augustine and Neher, 1992 Zucker, 1993 Heidelberger et al., 1994). 

At the distal tip of the axon are voltage-gated Ca2+ channels. When the wave of depolarization reaches these channels, they open, and Ca2+ enters from the extracellular space. The rise in cytoplasmic [Ca2+] then triggers release of acetylcholine by exocy-tosis into the synaptic cleft (step (3) in Fig. 12-5). Acetylcholine diffuses to the postsynaptic cell (another... 

In response to the change in membrane potential, voltage-gated Ca2+ channels in the plasma membrane open, allowing Ca2+ to flow into the cell this raises the cytosolic [Ca2+] enough to trigger insulin release by exocytosis. 

Calcium channels are a third major group of cation-selective channels.514 As pointed out in Box 6-D, calcium ions are involved in a very wide range of signaling functions. These are discussed in several places in this book. Several of these functions depend upon voltage-gated Ca2+ channels. Muscle is rich in L-type or DHP-sensitive channels (Box 6-D) which play a role in transmission of nerve impulses to muscles by allowing rapid flow of calcium ions into cells from outside.515... 

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