Referenced in: none

Automatically associated channels: Cav1.3

Title: Chronic morphine treatment decreases the Cav1.3 subunit of the L-type calcium channel.

Authors: Victoria L Haller, Marissa A Bernstein, Sandra P Welch

Journal, date & volume: Eur. J. Pharmacol., 2008 Jan 14 , 578, 101-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18048029

Abstract
Voltage-gated L- and N-type calcium channels (VOCs) are implicated in the activity of morphine, but their contribution to the expression of opioid tolerance remains uncertain. L- and N-type VOCs are heteropentamers of alpha(1), alpha(2)delta, beta, and gamma subunits. The alpha(1) subunit forms both the ion pore and the binding site for ligands. The Ca(v)1.2 and Ca(v)1.3 are the neuronal dihydropyridine (DHP)-sensitive L-type channel subunit types. The Ca(v)2.2 subunit is found in omega conotoxin GVIA-sensitive N-type calcium channels. Ca(v)1.2 VOC gating properties are phosphorylation-dependent with many kinases implicated. We hypothesized that changes in channel subunit structure or phosphorylation state, induced by chronic opioid exposure, may in part explain changes in calcium regulation observed both in vivo and in vitro. Antibodies, specific for the Ca(v)1.2, Ca(v)1.3, and Ca(v)2.2 subunits of VOCs were employed with Western immunoassays to access whether chronic morphine treatment had an effect on receptor protein levels. The L-type channel Ca(v)1.3 protein, but not the Ca(v)1.2 protein or phosphorylation state, significantly decreased upon chronic morphine treatment. The Ca(v)2.2 subunit protein of the N-type channel of VOCs remained unchanged. The Ca(v)1.3 subunit modification may represent one of many potential adaptive changes in tolerance to morphine-induced changes in intracellular calcium.