Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries.
The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1-100 microM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K(+) solution. K(+)-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co(2+) (100-200 microM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K(+)-induced contraction. In the presence of Co(2+) and in low-Na(+) solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca(2+) influx through voltage-dependent Ca(2+) channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca(2+) channels and Ca(2+) sensitization of the contractile process.
Gokina
N I
NI
Department of Pharmacology, College of Medicine, The University of Vermont, Burlington 05405, USA. gokina@salus.med.uvm.edu
Bevan
J A
JA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D002927:Cimetidine / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007477:Ions; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D012996:Solutions; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006635:Histamine H2 Antagonists; D007477:Ions; D012996:Solutions; D003035:Cobalt; D002927:Cimetidine; D006632:Histamine; D012964:Sodium; D009543:Nifedipine; D011188:Potassium