Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

Abstract

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 μM) 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 Co2+ (100–200 μM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K+-induced contraction. In the presence of Co2+ 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 Ca2+ influx through voltage-dependent Ca2+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 Ca2+channels and Ca2+ sensitization of the contractile process.