Carbon monoxide stimulates a potassium-selective current in rabbit corneal epithelial cells.
The effects of CO on ion currents in freshly dispersed rabbit corneal epithelial cells were assessed using the perforated patch whole cell voltage-clamp technique. Bath perfusion with 1% CO resulted in a 84 +/- 18% (mean +/- SE, n = 14) increase in potassium current (IK) and a membrane hyperpolarization from -42 +/- 4 to -51 +/- 4 mV. The CO-stimulated current reversed at -64 +/- 7 mV [reverse potential (EK) = -87 mV]. The stimulated current was blocked by 1 mM quinidine or 1 mM diltiazem, agents that inhibit IK in rabbit corneal epithelial cells. Single potassium-channel currents measured in the cell-attached configuration showed that exogenous CO increased the steady-state open probability from 0.003 to 0.156 at a holding potential of -40 mV. CO did not affect open probability in excised patches. The single-channel conductance measured from -40 to +40 mV was unaffected. Intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration measured with radioimmunoassay techniques was found to increase from 0.41 +/- 0.24 to 0.55 +/- 0.27 pmol/10(6) cells after the addition of 1% CO (P < 0.05). The data show that bath perfusion with exogenous CO activates IK and hyperpolarizes the resting membrane potential; the data also suggest that CO modulates intracellular cGMP concentration.
Rich
A
A
Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905.
Farrugia
G
G
Rae
J L
JL
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009994:Osmolar Concentration; D011188:Potassium / Q000502:physiology*; D026902:Potassium Channel Blockers; D011817:Rabbits
D026902:Potassium Channel Blockers; D002248:Carbon Monoxide; D006152:Cyclic GMP; D011188:Potassium