Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells

Potassium (K) channels play a significant role in modulating human corporal smooth muscle tone, and thus, erectile capacity. Recent pharmacological st udies indicate that the metabolically-regulated K channel (K-ATP) may be an important modulator of human penile erection with significant therapeutic potential. The goal of these initial studies, therefore, was to utilize pat ch clamp techniques to characterize the putative K-ATP subtype(s) present i n cultured and freshly isolated human corporal smooth muscle cells. In the cell-attached patch mode, two distinct unitary K+ currents were identified whose respective conductance values were similar in cultured and freshly is olated smooth muscle cells. In cultured myocytes, the measured conductance values in symmetric KCl (140 mM) solutions were 59.1 +/- 2.7 pS and 18.4 +/ - 2.1 pS (n = 5 cells). Under identical experimental conditions in freshly isolated myocytes, corresponding conductance values were 59.2 +/- 3.7 pS an d 18.5 +/- 2.4 pS, respectively (n = 4 cells). I-V curves constructed durin g step depolarization (-60 to +80 mV), revealed a linear I-V relationship f or both unitary conductances. Single channel records documented that both c onductances were reversibly inhibited by the application of ATP (1 - 3 mM) to the bath solution in the inside-out attached patch configuration. The un itary activity of both K channel subtypes was significantly increased by th e application of pinacidil (10 mu M) and levcromakalim (10 mu M). Whole cel l patch recordings documented a glibenclamide-sensitive, pinacidil- and lev cromakalim-induced increase in the whole cell outward K+ current during ste p depolarization ( - 70 mV to + 130 mV) of 105 +/- 37%, 139 +/- 42%, respec tively. These data confirm and extend our previous observations, and provid e the first evidence for the presence of K-ATP channel subtypes in human co rporal smooth muscle cells.