Transient activation of K+ channels by carbachol in bovine pigmented ciliary body epithelial cells.
The action of carbachol (CCh) on isolated pigmented ciliary epithelial cells was examined using whole cell patch-clamp recording. Application of 100 microM CCh caused transient, occasionally oscillatory, increases in the inward and outward currents, followed by a long-term decrease in both currents. Caffeine produced transient responses similar to those of CCh. The responses to CCh were blocked by the muscarinic receptor antagonist atropine and the inositol 1,4,5-trisphosphate receptor blocker heparin (200 micrograms/ml in patch pipette). Manipulation of the internal ionic concentrations indicated that only K+ conductances were affected by CCh. Changing intracellular Ca2+ concentration ([Ca2+]i) with the calcium ionophore ionomycin demonstrated that both the inward rectifier K+ current and the outward current exhibited Ca2+ dependence. There was no Cl- current stimulated either directly by CCh or indirectly by modulators of [Ca2+]i, and any Cl- currents present arose from osmotic effects. In the short term, muscarinic stimulation will activate K+ channels by causing a transient increase in [Ca2+]i. This effect only lasts for 1-5 min, however, and, in the long term, the conductance decreases below its original level. The effect of such a transient increase in [Ca2+]i on secretion would be complex, involving effects on gap junction communication between the pigmented and nonpigmented cell layers and the activation state of Cl- channels in the nonpigmented cells. This complexity probably accounts for the variable reports of the effects of muscarinic stimulation of the ciliary body in vivo.
Stelling
J W
JW
Physiology Unit, School of Molecular and Medical Biosciences, University of Wales, Cardiff, United Kingdom.
Jacob
T J
TJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D002924:Ciliary Body / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D010858:Pigmentation; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011930:Reaction Time
D015221:Potassium Channels; D002110:Caffeine; D001285:Atropine; D002217:Carbachol; D006493:Heparin; D002118:Calcium