Smooth muscle cell transient receptor potential polycystin (TRPP)2 channels contribute to the myogenic response in cerebral arteries

Abstract

Intravascular pressure‐induced vasoconstriction is a smooth muscle cell (myocyte)‐specific mechanism that controls systemic blood pressure and regional organ blood flow. Myocyte polycystin (TRPP)‐1 and ‐2 proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined myocyte TRPP2 expression, cellular distribution, cation currents (ICat), and contribution to the myogenic response in cerebral arteries. Real‐time RT‐PCR amplified transcripts for TRPP1 and TRPP2, with TRPP2 being the predominant message in isolated rat cerebral artery myocytes. Western blot analysis indicated that TRPP2 protein was present in rat and human cerebral arteries. Arterial surface biotinylation and immunofluorescence indicated that TRPP2 is located primarily within the myocyte plasma membrane. Cell swelling induced by hyposmotic bath solution stimulated ICat in myocytes that were inhibited by RNAi‐mediated selective TRPP2 channel knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced myogenic tone at pressures between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter membrane depolarization‐induced (60 mmol/L K+) vasoconstriction. These data indicate that TRPP2 contributes to stretch‐activated ICat in myocytes of resistance‐size cerebral arteries, leading to vasoconstriction. NIH/NHLBI.