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 (I(K)) and a membrane hyperpolarization from -42 ± 4 to -51 ± 4 mV. The CO-stimulated current reversed at -64 ± 7 mV [reverse potential (E(K)) = -87 mV]. The stimulated current was blocked by 1 mM quinidine or 1 mM diltiazem, agents that inhibit I(K) 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/10⁶ cells after the addition of 1% CO (P < 0.05). The data show that bath perfusion with exogenous CO activates I(K) and hyperpolarizes the resting membrane potential; the data also suggest that CO modulates intracellular cGMP concentration.