Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCα in arterial myocytes

Sendoa Tajada, Claudia M. Moreno, O. Samantha, Sean Woods, Daisuke Sato, Manuel F Navedo, Luis Fernando Santana

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca2+ influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (Angll). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150. Here, we used super-resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and mathematical modeling approaches to test the hypothesis that AKAP150-dependent modulation of TRPV4 channels is critically dependent on the distance between these two proteins in the sarcolemma of arterial myocytes. Our data show that the distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial bed. Consistent with our hypothesis, we further find that basal and AnglI-induced TRPV4 channel activity decays exponentially as the distance between TRPV4 and AKAP150 increases. Our data suggest a maximum radius of action of ~200 nm for local modulation of TRPV4 channels by AKAP150-associated PKCα.

Original languageEnglish (US)
Pages (from-to)639-659
Number of pages21
JournalJournal of General Physiology
Volume149
Issue number6
DOIs
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Physiology

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