Ligand-gated Ca2 channels

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. 

Intracellular, ER-located, ligand-gated Ca2+ channels include the inositol-1,4,5-triphosphate (IP3) receptor, the ryanodine receptor (RyR), the NAADP receptor and the sphingolipid receptor [157-159]. The IP3 receptor Ca2+ channel is opened by IP3 generated as a result of G protein-(or RTK)-mediated PLC activation [159]. 

In skeletal muscle open voltage-gated L-type Ca2+ channels can interact directly with muscle ER (sarcoplasmic reticulum) ryanodine receptors to open the ryanodine receptor Ca2+ channel and thence elevate cytosolic Ca2+ concentration from sarcoplamic. reticulum Ca2+ stores. However in neurons and cardiac muscle activation of PM voltage-gated Ca2+ channels indirectly activates ryanodine receptor Ca2+ channels as outlined in the section on Ligand-gated Ca2+ channels . 

Table 4.4 Voltage- and ligand-gated Ca2+ channels and Na+/Ca2+ antiporter ...

Mobilization of Ca2+ from the Ca2+ stores of the endoplasmic reticulum takes place with the help of Ca2+ channels, of which two types stand out the InsPi receptors and the ryanodin receptors. Both are ligand-gated Ca2+ channels, in which receptor and ion channel form a structural unit. The InsP3 receptors and ryanodin receptors are localized in the endoplasmic and sarcoplasmic reticulum, respectively, and may be opened during the process of signal transduction (Fig. 6.8). 

Synaptic Transmission. Figure 1 Synaptic transmission. The presynaptic terminal contains voltage-dependent Na Superscript and Ca2+ channels, vesicles with a vesicular neurotransmitter transporter VNT, a plasmalemmal neurotransmitter transporter PNT, and a presynaptic G protein-coupled receptor GPCR with its G protein and its effector E the inset also shows the vesicular H+ pump. The postsynaptic cell contains two ligand-gated ion channels LGIC, one for Na+ and K+ and one for Cl-, a postsynaptic GPRC, and a PNT. In this synapse, released transmitter is inactivated by uptake into cells. 

Ca2+, raising the possibility that the activity of ligandgated ion channels can also modulate the MAPK pathway. However, to date, there is no evidence to suggest that this regulation is reciprocal, that is, that activation of the MAPK pathway can modulate the activity of either GPCRs or ligand-gated ion channels. 

The addition of CaBPs can directly activate the IP3-R in a Ca2+-dependent manner, via interaction with the N-terminus region of the receptor. This raises the possibility that CaBPs can act on IP3-Rs to potentiate the Ca2+ signals that arise from other sources, e.g. ligand-gated ion channels. 

Among the seven families of serotonin receptors, only the 5-HT3 receptors are ligand-gated ion channels, whereas all others are G protein-coupled receptors (Barnes and Sharp 1999). 5-HT3 receptors are rather unselective cation channels with a high permeability for Ca2+ (Ronde and Nichols 1998). In the central nervous system, they are expressed abundantly in the neocortex, the anterior olfactory nucleus, the hippocampus, and the amygdala. In addition, 5-HT3 receptors are present in the caudate putamen and the nucleus accumbens, and, at high levels, in the brain stem (Parker et al. 1996 Morales et al. 1998 Chameau and van Hooft 2006). 

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