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 3x10(-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.
Burt
Richard P
RP
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom. r.burt@ucl.ac.uk
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D007552:Isotonic Solutions / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D007211:Indoles; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid