Depletion of Ca2+ from intracellular stores of the rat portal vein stimulates a tonic contraction

The possibility that Ca2+ store depletion can stimulate contraction of the rat portal vein was investigated in functional experiments. Ca2+ stores were depleted with phenylephrine or cyclopiazonic acid in the absence of extracellular Ca2+ and then washed out for 30 min. Upon re-addition of extracellular Ca2+, a tonic contraction was produced, showing the stimulus for contraction was Ca2+ store depletion. The contractions were abolished by niflumic acid and nifedipine however, indicating they were dependent on depolarization resulting from opening of Ca2+-activated Cl− channels and Ca2+ influx through voltage-gated channels. Cumulative additions of phenylephrine below 3×10−6 M did not produce tonic contractions but did in high K+ Krebs solution, where levcromakalim had no effect. This showed the tonic contractions were initially prevented by K+ channel opening. Increased Ca2+ entry through voltage-gated channels may therefore stimulate Ca2+-activated Cl− channels. Ca2+ store depletion could stimulate this by opening store-operated non-selective cation channels, resulting in depolarization.