Referenced in: none

Automatically associated channels: Slo1 , TRP , TRPM , TRPM4

Title: Basal protein kinase Cδ activity is required for membrane localization and activity of TRPM4 channels in cerebral artery smooth muscle cells.

Authors: Zarine I Garcia, Allison Bruhl, Albert L Gonzales, Scott Earley

Journal, date & volume: Channels (Austin), 2011 May-Jun , 5, 210-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21406958

Abstract
The melastatin (M) transient receptor potential channel (TRP) channel TRPM4 is a critical regulator of vascular smooth muscle cell membrane potential and contractility. We recently reported that PKCδ activity influences smooth muscle cell excitability by promoting translocation of TRPM4 channel protein to the plasma membrane. Here we further investigate the relationship between membrane localization of TRPM4 protein and channel activity in native cerebral arterial myocytes. We find that TRPM4 immunolabeling is primarily located at or near the plasma membrane of freshly isolated cerebral artery smooth muscle cells. However, siRNA mediated downregulation of PKCδ or brief (15 min) inhibition of PKCδ activity with rottlerin causes TRPM4 protein to move away from the plasma membrane and into the cytosol. In addition, we find that PKCδ inhibition diminishes TRPM4-dependent currents in smooth muscle cells patch clamped in the amphotericin B perforated patch configuration. We conclude that TRPM4 channels are mobile in native cerebral myocytes and that basal PKCδ activity supports excitability of these cells by maintaining localization TRPM4 protein at the plasma membrane.