Modulation of calcium movements by nitroprusside in isolated vascular smooth muscle cells.
Using the patch-clamp technique, we have characterised the inward current from enzymatically dispersed rabbit pulmonary arterial cells, and investigated the effects of the vasodilator, nitroprusside (NP), on these and other membrane currents. With Cs(+)-filled pipettes, inward currents were recorded during brief depolarizing voltage steps in both physiological Ca2+ and 10 mM Ba2+. The threshold for current activation was positive to -40 mV and the current peaked at 0 mV for Ca2+ and +10 mV for Ba2+. During the first few minutes of recording, inward currents increased or "ran-up". This could not be attributed to blockade of outward current or the inclusion of adenosine triphosphate (ATP) in the patch pipette. Experiments revealed that all the inward current was carried through a single type of voltage-activated Ca2+ channel, namely the high-threshold, dihydropyridine-sensitive channel. It was unaffected by tetrodotoxin but was abolished at all potentials by low concentrations of Cd2+ (100 microM) or nifedipine (1-2 microM). NP (1 microM) suppressed peak inward Ba2+ current at +10 mV by approximately 45%. Higher concentrations (50 microM) did not produce further blockade of the current. This decrease was associated with increased inactivation of the current, and both effects required the presence of ATP in the patch pipette. In physiological Ca2+, using K(+)-filled pipettes, NP was found to induce spontaneous bursts of outward currents, which are probably activated by the release of Ca2+ from Ca(2+)-overloaded stores. These results are consistent with NP lowering cytosolic Ca2+, and hence causing vasodilation, by inhibiting Ca2+ influx through voltage-gated Ca2+ channels and by promoting Ca2+ uptake into the sarcoplasmic reticulum.
Clapp
L H
LH
Department of Pharmacology, United Medical School, St Thomas's Hospital, London, UK.
Gurney
A M
AM
D000818:Animals; D001464:Barium / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D004594:Electrophysiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology*
D009599:Nitroprusside; D001464:Barium; D002118:Calcium