Discrete store-operated calcium influx into an intracellular compartment in rabbit arteriolar smooth muscle.
This study tested the hypothesis that store-operated channels (SOCs) exist as a discrete population of Ca2+ channels activated by depletion of intracellular Ca(2+) stores in cerebral arteriolar smooth muscle cells and explored their direct contractile function. Using the Ca2+ indicator fura-PE3 it was observed that depletion of sarcoplasmic reticulum (SR) Ca2+ by inhibition of SR Ca2+-ATPase (SERCA) led to sustained elevation of [Ca2+]i that depended on extracellular Ca2+ and slightly enhanced Mn2+ entry. Enhanced background Ca2+ influx did not explain the raised [Ca2+]i in response to SERCA inhibitors because it had marked gadolinium (Gd3+) sensitivity, which background pathways did not. Effects were not secondary to changes in membrane potential. Thus SR Ca2+ depletion activated SOCs. Strikingly, SOC-mediated Ca2+ influx did not evoke constriction of the arterioles, which were in a resting state. This was despite the fura-PE3-indicated [Ca2+]i rise being greater than that evoked by 20 mM [K+]o (which did cause constriction). Release of endothelial vasodilators did not explain the absence of SOC-mediated constriction, nor did a change in Ca2+ sensitivity of the contractile proteins. We suggest SOCs are a discrete subset of Ca2+ channels allowing Ca2+ influx into a 'non-contractile' compartment in cerebral arteriolar smooth muscle cells.
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
R
R
Flemming
A
A
Cheong
A M
AM
Dedman
D J
DJ
Beech
D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D019284:Thapsigargin; D002118:Calcium; C000543:cyclopiazonic acid