Relaxation of the corpus cavernosum smooth muscle is an absolute prerequisite for penile erection. Potassium channels play a role in the physiologic regulation of corporal smooth muscle tone. In spite of the physiological importance of K ATP channel in the modulation of corporal smooth muscle tone, there is a shortage of information available about the K ATP channel subtype(s) present in the corporal smooth muscle. The purpose of this study was to investigate the subunit type of K ATP channel, that is, the combinations of the Kir subunit and the SUR subunit in the human corporal smooth muscle and determine whether the electrophysiological kinetics and pharmacological properties of K ATP channels meet the subunit characteristics of the ion channel. We used cultured human corporal smooth muscle cells. To determine the presence of Kir and SURs subunits, RT-PCR was performed using Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B gene-specific primers. For electrophysiological recordings, the whole-cell, inside-out, and cell-attached configurations of the patch-clamp technique were used. We observed transcripts for Kir6.1, Kir6.2, and SUR2B in mRNA isolated from smooth muscle cells of cultured human corpus carvernosum. We recorded the unitary K ATP channel under the condition of intracellular and extracellular 140 mM [K + ], and the slope conductance of the channel was 42.0 7 2.6 pS which is an intermediate conductance between that of either Kir6.1 or Kir6.2. The pinacidil (10 lM) increased the magnitude of the outward K + current (214.6 7 89.2%, n ¼ 12, Po0.05), which was blocked by the subsequent addition of the specific K ATP channel subtype selective blocker, glibenclamide (10 lM). The SIN-1(200 lM) induced increases in whole-cell outward K + currents (126.0 7 1.4%, n ¼ 4). The increased currents by SIN-1 were inhibited by glibenclamide (10 lM). We are the first to show that K ATP channel in human corporal smooth muscle is composed of Kir6.1-Kir6.2 construct expressed with SUR2B by RT-PCR. These findings, taken together with the electrophysiological results, suggest that K ATP channel in corporal smooth muscle cells is composed of heteromultimers of Kir6.1 and Kir6.2 with the ratio of 3 : 1 or 4 : 0 and SUR2B.

Ginseng was known to be an effective natural product that enhances penile erection. However, the precise biological function and mechanisms of action of ginseng with regard to erectile function remain unknown. The principal objective of this study was to identify ginsenoside (principal molecular ingredients of ginseng)-induced activation of large-conductance K Ca channel in human corporal smooth muscle cells, and to determine ginseng's mechanism of action on penile erection. Electrophysiological studies using cultured human corporal smooth muscle cells were conducted. We evaluated the effects of total ginsenosides (TGS) and ginsenoside Rg3 on large-conductance K Ca channel by determining whole-cell currents and single-channel activities. There was an increase in outward current dependent on TGS concentration (at þ 60 mV, 1 lg ml À1; 168.3±59.3%, n ¼ 6, Po0.05, 10 lg ml À1; 173.2±36.8%, n ¼ 4, Po0.05, 50 lg ml À1; 295.3±62.3%, n ¼ 19, Po0.001, 100 lg ml À1 ; and 462.3 ± 97.1%, n ¼ 5, Po0.001) and Rg3 concentration (at þ 60 mV, 1 lM (0.78 lg ml À1 ); 222.8 ± 64.8%, n ¼ 11, Po0.0001, 10 lM; 672.6 ± 137.1%, n ¼ 10, Po0.0001, 50 lM; and 1713.3±234.7%, n ¼ 15, Po0.001) in the solution that was blocked completely by tetraethylammonium (TEA). Channel opening in cell-attached mode and channel activity in the inside-out membrane patches was also increased significantly by 50 lg of TGS or 10 lM of Rg3. The results of this study suggested that the activation of large-conductance K Ca channels by ginsenoside could be one mechanism of ginsenoside-induced relaxation in corporal smooth muscle.