Regulation of the cytosolic Ca2+ concentration by Ca2+ stores in single smooth muscle cells from rat cerebral arteries.
1. There is no general agreement on the presence or role of Ca(2+)-induced Ca2+ release in smooth muscle. In this paper, Ca(2+)-induced Ca2+ release has been investigated in rat resistance-sized superior cerebral arteries to determine its role in regulating the cytosolic Ca2+ concentration ([Ca2+]i). 2. Pressurized superior cerebral arteries developed spontaneous oscillations in diameter. These oscillations were abolished by ryanodine (an inhibitor of Ca(2+)-induced Ca2+ release) and removal of extracellular Ca2+. This suggests, indirectly, that Ca(2+)-induced Ca2+ release may regulate [Ca2+]i in the resistance arteries. 3. To determine if Ca(2+)-induced Ca2+ release could regulate [Ca2+]i, single smooth muscle cells were isolated from the superior cerebral artery, voltage clamped in the whole cell configuration and high temporal resolution [Ca2+]i measurements made. The relationship between the Ca2+ current (ICa) and rise in [Ca2+]i was examined. 4. Depolarization triggered ICa and increased [Ca2+]i. The time course of the measured increase in [Ca2+]i closely followed the increase in [Ca2+]i expected from the time-integrated ICa, although about 140-fold more Ca2+ entered the cytosol than appeared as free Ca2+. When the cells were dialysed with ryanodine (30 microM), the Ca2+ transient evoked by the ICa was substantially reduced indicating that Ca2+ influx triggered Ca2+ release from an internal store. 5. Voltage pulses to negative membrane potentials were more effective in triggering Ca2+ release than pulses to positive potentials suggesting that the Ca(2+)-induced Ca2+ release was voltage dependent. However, the release of Ca2+ from the internal store triggered by caffeine was voltage independent. These results suggest that the voltage dependence of Ca2+ release is indirect and possibly related to the plasmalemma unitary Ca2+ current magnitude. 6. The results establish that Ca(2+)-induced Ca2+ release contributes to depolarization-evoked increases in [Ca2+]i in rat resistance-sized superior cerebral arteries over the physiological [Ca2+]i range (100-200 nM). Compared with more positive membrane potentials the efficacy of Ca2+ in triggering release is high at physiological membrane potentials.
Kamishima
T
T
Division of Neuroscience and Biomedical Systems, University of Glasgow, UK.
McCarron
J G
JG
D000818:Animals; D002021:Buffers; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
D002021:Buffers; D002121:Calcium Channel Blockers; D012433:Ryanodine; D002110:Caffeine; D009553:Nimodipine; D002118:Calcium