Intraluminal pressure triggers myogenic response via activation of calcium spark and calcium-activated chloride channel in rat renal afferent arteriole

Kay Pong Yip, Lavanya Balasubramanian, Chen Kan, Lei Wang, Ruisheng Liu, Luisa Ribeiro-Silva, James Sham

Research output: Contribution to journalArticle

Abstract

Myogenic contraction of renal arterioles is an important regulatory mechanism for renal blood flow autoregulation. We have previously demonstrated that integrin-mediated mechanical force increases the occurrence of Ca2‒ sparks in freshly isolated renal vascular smooth muscle cells (VSMCs). To further test whether the generation of Ca2‒ sparks is a downstream signal of mechanotransduction in pressure-induced myogenic constriction, the relationship between Ca2‒ sparks and transmural perfusion pressure was investigated in intact VSMCs of pressurized rat afferent arterioles. Spontaneous Ca2‒ sparks were found in VSMCs when afferent arterioles were perfused at 80 mmHg. The spark frequency was significantly increased when perfusion pressure was increased to 120 mmHg. A similar increase of spark frequency was also observed in arterioles stimulated with α1-integrin-activating antibody. Moreover, spark frequency was significantly higher in arterioles of spontaneous hypertensive rats at 80 and 120 mmHg. Spontaneous membrane current recorded using whole cell perforated patch in renal VSMCs showed predominant activity of spontaneous transient inward currents instead of spontaneous transient outward currents when holding potential was set close to physiological resting membrane potential. Real-time PCR and immunohistochemistry confirmed the expression of Ca2‒-activated Cl channel (ClCa) TMEM16A in renal VSMCs. Inhibition of TMEM16A with T16Ainh-A01 impaired the pressure-induced myogenic contraction in perfused afferent arterioles. Our study, for the first time to our knowledge, detected Ca2‒ sparks in VSMCs of intact afferent arterioles, and their frequencies were positively modulated by the perfusion pressure. Our results suggest that Ca2‒ sparks may couple to ClCa channels and trigger pressure-induced myogenic constriction via membrane depolarization.

Original languageEnglish (US)
Pages (from-to)F1592-F1600
JournalAmerican Journal of Physiology - Renal Physiology
Volume315
Issue number6
DOIs
StatePublished - Dec 1 2018

    Fingerprint

Keywords

  • Afferent arteriole
  • Confocal fluorescence microscopy
  • Integrin
  • Myogenic response
  • TMEM16A

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this