Phasic contractions of the rat portal vein depend on intracellular Ca2+ release stimulated by depolarization

The phasic contraction to phenylephrine of the rat isolated portal vein was investigated using functional studies. Phasic contractions to phenylephrine and caffeine could be produced after several minutes in Ca2+-free Krebs solution, which were inhibited by cyclopiazonic acid or ryanodine. The phenylephrine and caffeine contractions were abolished, however, within 10 min in Ca2+-free Krebs solution and by nifedipine. This indicated the Ca2+ stores were depleted in the absence of Ca2+ influx through voltage-gated channels. The phasic contraction to phenylephrine was also abolished by niflumic acid even in Ca2+-free Krebs solution. This showed that the response depended on intracellular Ca2+ release stimulated directly by depolarization, resulting from opening of Ca2+-activated Cl- channels, but did not require Ca2+ influx. In support of this, K+-induced phasic contractions were also produced in Ca2+-free Krebs solution. The phenylephrine but not K+-induced phasic contractions in Ca2+-free Krebs solution were inhibited by ryanodine or cyclopiazonic acid. This would be consistent with Ca2+ release from more superficial intracellular stores (affected most by these agents), probably by inositol 1,4,5-trisphospate, being required to stimulate the phenylephrine depolarization.