title: 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.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. jjagger@physiol1.utmem.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Jaggar
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006706:Homeostasis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D012433:Ryanodine; D019284:Thapsigargin; D004110:Diltiazem; D002118:Calcium