CELIKALIM (WAY-120491) INCREASES K+ OUTWARD FLUX IN DOG AND HUMAN AIRWAY SMOOTH-MUSCLE

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 (110 pM) enhanced the rate of 86Rb+ efflux from dog airway smooth muscle in a concentration-dependent manner. At 1 pM, the rate of 86Rb+ efflux was enhanced by 25% in human airway smooth muscle cells. In current recordings, celikalim (1 pM) 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. © 1994, Academic Press. All rights reserved.