Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

• DOI: 10.1085/jgp.201311050
• Publication Date: 2014-04-28T18:42:48Z
• Authors: Jose Mercado; Rachael Baylie; Manuel F. Navedo; Can Yuan; John D. Scott; Mark T. Nelson; Joseph E. Brayden; Luis F. Santana
• Keywords: TRPV4

Transient receptor potential vanilloid 4 (TRPV4) channels are Ca2+-permeable, nonselective cation expressed in multiple tissues, including smooth muscle. Although TRPV4 play a key role regulating vascular tone, the mechanisms controlling Ca2+ influx through these arterial myocytes poorly understood. Here, we tested hypothesis that anchoring protein AKAP150 and kinase C (PKC) critical regulation of during angiotensin II (AngII) signaling. Super-resolution imaging revealed gathered into puncta variable sizes along sarcolemma myocytes. Recordings entry via single (“TRPV4 sparklets”) suggested basal sparklet activity was low. However, elementary sparklets ∼100-fold greater than L-type CaV1.2 channel sparklets. Application agonist GSK1016790A or vasoconstrictor AngII increased specific regions cells. PKC were required for AngII-induced increases activity. interactions dynamic; activation signaling proximity Furthermore, local stimulation diacylglycerol by laser light-sensitive Gq-coupled (opto-α1AR) resulted TRPV4-mediated influx. We propose AKAP150, PKC, form dynamic subcellular domains control