title: Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C.
abstract: Ca(2+) influx via L-type Ca(2+) 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 kinase C (PKC). One of the prominent pathways of PKC activation in cardiac and smooth muscle cells is via activation of Gq-coupled receptors and subsequent activation of protein lipase C (PLC). CaV1.2 was shown to be modulated, phosphorylated by, and associated with PKC both in vitro and in vivo. Despite the well documented enhancing effect of vasoconstrictors operating via Gq on CaV1.2 channels, the molecular mechanism by which PKC affects the channel has not yet been resolved. Furthermore, the nature of PKC modulation of CaV1.2 appears to be species-, age- and tissue-dependent. Results from experiments in heterologous expression systems are often contradicting and are difficult to coalesce. The choice of both the heterologous expression system and the CaV1.2 isoform expressed are at the core of this conundrum. Complete reconstitution of the enhancing effect of PKC was successful only in Xenopus oocytes and only when the long N-terminus (NT) isoform of the channel was expressed. This review summarizes past and new findings regarding the mechanism by which activated PKC modulates CaV1.2 channels in native tissues and heterologous expression systems, and suggests perspectives for future research.
authors.forename: Sharon
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. lahavsha@post.tau.ac.il.
authors.forename: Nathan
authors.initials: N
authors.lastname: Dascal
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D043562:Receptors, G-Protein-Coupled; D011493:Protein Kinase C