Celikalim (WAY-120491) Increases K⁺ Outward Flux in Dog and Human Airway Smooth Muscle

Abstract

Summary: The ability of the potassium channel opener celikalim (WAY-120491) to increase potassium conductance in airway smooth muscle cells was investigated. The rate of ⁸⁶Rb⁺ efflux was measured from dog trachealis muscle strips and human trachealis smooth muscle cells in culture. Whole-cell currents were recorded from dog trachealis smooth muscle cells freshly dissociated using the nystatin-perforated patch technique. Celikalim (1-10 μM) enhanced the rate of ⁸⁶Rb⁺ efflux from dog airway smooth muscle in a concentration-dependent manner. At 1 μM, the rate of ⁸⁶Rb⁺ efflux was enhanced by 25% in human airway smooth muscle cells. In current recordings, celikalim (1 μM) elicited a glyburide-sensitive outward current, increasing the steady-state current from 367±20 pA to 688±172 pA at +20 mV (n=5). At -60 mV, a voltage closer to the resting potential, the holding current was increased by only +26±15 pA (n=5). This smaller increase was sufficient to hyperpolarize the membrane by 8 mV. These results indicate that celikalim is a potent potassium channel opener in dog and human airway smooth muscles. The present data support the hypothesis that an increase in resting K⁺ conductance by potassium channel openers may account for their relaxing effect in airway smooth muscles.