Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C

Title:Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C

Volume: 8

Author(s): Sharon Weiss and Nathan Dascal

Affiliation:

Keywords: Calcium channel, heart, isoform, molecular mechanism, protein kinase C, smooth muscle.

Abstract: Ca²⁺ influx via L-type Ca²⁺ channel (L-VDCC; Ca_V1.2) 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. Ca_V1.2 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). Ca_V1.2 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 Ca_V1.2 channels, the molecular mechanism by which PKC affects the channel has not yet been resolved. Furthermore, the nature of PKC modulation of Ca_V1.2 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 Ca_V1.2 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 Ca_V1.2 channels in native tissues and heterologous expression systems, and suggests perspectives for future research.

Cite this article as:

Weiss Sharon and Dascal Nathan, Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C, Current Molecular Pharmacology 2015; 8 (1) . https://dx.doi.org/10.2174/1874467208666150507094733