Effect of the stable thromboxane derivative, carbocyclic thromboxane A2, on membrane potential of rat myenteric neurones in culture.
The effects of carbocyclic thromboxane A(2) (cTXA(2); 10(-6) mol L(-1)) on membrane potential and cytosolic Ca(2+) concentration were measured with the whole-cell patch-clamp or the fura-2 method, respectively, at rat myenteric ganglia. cTXA(2) caused a hyperpolarization of myenteric neurones from -19.3 +/- 2.5 to -29.3 +/- 2.3 mV. In addition, the eicosanoid potentiated the carbachol-induced depolarization from 4.2 +/- 1.0 mV under control conditions to 11.1 +/- 1.1 mV in the presence of the cTXA(2) (n = 9). The hyperpolarization was abolished by internal application of CsCl (140 mmol L(-1)), a non-selective blocker of K(+) channels, or EGTA (11 mmol L(-1)in the pipette solution), a chelator of intracellular Ca(2+). A similar inhibition was observed in the presence of charybdotoxin (10(-7) mol L(-1)). Fura-2 imaging experiments revealed a cTXA(2)-evoked increase in the intracellular Ca(2+) concentration as indicated by a rise in the fura-2 ratio signal. This response was mediated by a release of Ca(2+) from intracellular stores as sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase blockade with cyclopiazonic acid (5 x 10(-5) mol L(-1)) completely abolished the response to cTXA(2). A similar inhibition was observed after blockade of phospholipase C with U-73122 (10(-5) mol L(-1)). These results suggest an activation of Ca(2+)-activated K(+) channels by cTXA(2) after stimulation of phospholipase C.
Rehn
M
M
Institute for Veterinary Physiology, University of Giessen, Germany.
Diener
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009197:Myenteric Plexus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D011760:Pyrrolidinones; D014662:Vasoconstrictor Agents; C024587:thromboxane A2, carbocyclic; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D013928:Thromboxane A2; D002118:Calcium