Actin cytoskeletal modulation of pressure-induced depolarization and Ca(2+) influx in cerebral arteries.

The objective of this study was to examine the role of the actin cytoskeleton in the development of pressure-induced membrane depolarization and Ca(2+) influx underlying myogenic constriction in cerebral arteries. Elevating intraluminal pressure from 10 to 60 mmHg induced membrane depolarization, increased intracellular cytosolic Ca(2+) concentration ([Ca(2+)](i)) and elicited myogenic constriction in both intact and denuded rat posterior cerebral arteries. Pretreatment with cytochalasin D (5 microM) or latrunculin A (3 microM) abolished constriction but enhanced the [Ca(2+)](i) response; similarly, acute application of cytochalasin D to vessels with tone, or in the presence of 60 mM K(+), elicited relaxation accompanied by an increase in [Ca(2+)](i). The effects of cytochalasin D were inhibited by nifedipine (3 microM), demonstrating that actin cytoskeletal disruption augments Ca(2+) influx through voltage-sensitive L-type Ca(2+) channels. Finally, pressure-induced depolarization was enhanced in the presence of cytochalasin D, further substantiating a role for the actin cytoskeleton in the modulation of ion channel function. Together, these results implicate vascular smooth muscle actin cytoskeletal dynamics in the control of cerebral artery diameter through their influence on membrane potential as well as via a direct effect on L-type Ca(2+) channels.