The role of membrane depolarization in the contractile response of the rabbit basilar artery to 5-hydroxytryptamine.

1. 5-Hydroxytryptamine (5-HT, 10(-9)-10(-4) M) depolarized and contracted smooth muscle cells (resting potential: -69.1 +/- 0.9 mV, n = 112) in isolated cylindrical segments of the rabbit basilar artery. 2. Simultaneous measurement of membrane potential and wall tension (n = 43, thirteen vessels) showed that the onset of 5-HT-induced depolarization coincided with the onset of smooth muscle contraction in the majority of cells studied. In addition, the onset of relaxation which followed the wash-out of 5-HT always preceded the onset of membrane repolarization by 52 +/- 8 s (n = 14). 3. In 30% of smooth muscle cells exposed to concentrations of 5-HT greater than 10(-6) M, fast rhythmic depolarizations (amplitude 10-20 mV) were superimposed on the developing depolarization. Rhythmic membrane depolarization was always followed by rhythmic smooth muscle contraction, which peaked 2-4 s after the peak of the fast depolarization. 4. Muscle contraction, but not depolarization, produced with concentrations of 5-HT greater than 10(-7) M, was significantly increased by the removal of intimal-endothelial cells. 5. Smooth muscle depolarization recorded in the presence of increased extracellular K+ (greater than 5.2 mM) preceded the onset of smooth muscle contraction. For a similar change in membrane potential produced with either increased extracellular K+ or 5-HT, the corresponding increase in arterial wall tension was always greater with 5-HT. 6. The depolarization and contraction induced by 5-HT was markedly reduced or abolished if extracellular Na+ was totally replaced, isosmotically, with either sucrose or Tris at pH 7.4. Normal-sized contraction, but not depolarization, was recorded with 5-HT in Na+-free Tris solution at pH 8. 7. These observations suggest that 5-HT-stimulated contraction in cerebrovascular smooth muscle is largely a result of mechanisms other than depolarization of the smooth muscle cell membrane which it produces. However, high concentrations of 5-HT (greater than 10(-6) M) can stimulate additional depolarization, which has a faster time course and rhythmic nature. Discrete depolarizations of this type are responsible for initiating additional, phasic smooth muscle contractions.