Adrenergic regulation of calcium-activated potassium current in cultured rabbit pigmented ciliary epithelial cells.
1. The effects of adrenergic agonists on K+ currents were studied in cultured rabbit pigmented ciliary epithelial (PCE) cells. 2. Outward K+ current (IK) was reduced by tetraethylammonium chloride, the Ca2+-activated K+ (K(Ca)) channel blocker iberiotoxin (IbTX), or Ca2+-free external Ringer solution. The calcium ionophore ionomycin increased an IbTX-sensitive IK in PCE cells. 3. The adrenergic agonists adrenaline and phenylephrine increased IK in PCE cells. The induced current was blocked by IbTX and the alpha1-antagonist prazosin, suggesting that adrenergic agonists activate IK(Ca) via alpha1-adrenoreceptors. 4. Internal dialysis of D-myo-inositol 1,4, 5-trisphosphate (IP3) increased IK, whilst pre-incubation of PCE cells with thapsigargin or the phospholipase C (PLC) inhibitor U-73122 reduced phenylephrine-induced increases in IK(Ca). Adrenergic increases in IK(Ca) were mediated by a pertussis toxin-insensitive G protein. 5. These results demonstrate that IK(Ca) channels in rabbit PCE cells are coupled to alpha1-adrenergic receptors and a PLC/IP3 signalling pathway. Activation of these channels may modulate fluid secretion by the ciliary epithelium.
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
J S
JS
Ryan
Q P
QP
Tao
M E
ME
Kelly
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004963:Estrenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011224:Prazosin / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology; D015398:Signal Transduction; D019789:Tetraethylammonium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D004963:Estrenes; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D012604:Scorpion Venoms; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010656:Phenylephrine; D015759:Ionomycin; D019789:Tetraethylammonium; D019284:Thapsigargin; C064719:iberiotoxin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000252:Calcium-Transporting ATPases; D011224:Prazosin; D004837:Epinephrine