Intravascular pressure regulates local and global Ca(2+) signaling in cerebral artery smooth muscle cells.

Abstract

The regulation of intracellular Ca(2+) signals in smooth muscle cells and arterial diameter by intravascular pressure was investigated in rat cerebral arteries (approximately 150 microm) using a laser scanning confocal microscope and the fluorescent Ca(2+) indicator fluo 3. Elevation of pressure from 10 to 60 mmHg increased Ca(2+) spark frequency 2.6-fold, Ca(2+) wave frequency 1.9-fold, and global intracellular Ca(2+) concentration ([Ca(2+)](i)) 1.4-fold in smooth muscle cells, and constricted arteries. Ryanodine (10 microM), an inhibitor of ryanodine-sensitive Ca(2+) release channels, or thapsigargin (100 nM), an inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, abolished sparks and waves, elevated global [Ca(2+)](i), and constricted pressurized (60 mmHg) arteries. Diltiazem (25 microM), a voltage-dependent Ca(2+) channel (VDCC) blocker, significantly reduced sparks, waves, and global [Ca(2+)](i), and dilated pressurized (60 mmHg) arteries. Steady membrane depolarization elevated Ca(2+) signaling similar to pressure and increased transient Ca(2+)-sensitive K(+) channel current frequency e-fold for approximately 7 mV, and these effects were prevented by VDCC blockers. Data are consistent with the hypothesis that pressure induces a steady membrane depolarization that activates VDCCs, leading to an elevation of spark frequency, wave frequency, and global [Ca(2+)](i). In addition, pressure induces contraction via an elevation of global [Ca(2+)](i), whereas the net effect of sparks and waves, which do not significantly contribute to global [Ca(2+)](i) in arteries pressurized to between 10 and 60 mmHg, is to oppose contraction.