Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells.
The large conductance calcium-sensitive potassium channel (KCa or maxi-K) is an important modulator of human corporal smooth muscle tone, and therefore, erectile capacity. The goal of this investigation was to evaluate the actions of prostaglandin E1 (PGE1), the most widely used and effective drug for the treatment of impotence, on the activity of the KCa channel, a prominent K+ current present in human corporal smooth muscle. Whole-cell patch clamp studies conducted on short-term cultured and enzymatically dissociated human corporal smooth muscle cells, revealed mean resting potentials of -50.8 +/- 2.1 mV (n = 8) and -34 +/- 4 mV (n = 8), respectively. In the attached-patch configuration, the corresponding single-channel slope conductance values for the KCa channel subtype were 173 +/- 4 pS (n = 8) in cultured cells, and 190 +/- 13 pS (n = 3) in freshly isolated myocytes. Furthermore, voltage clamp experiments revealed that relative to control values, the application of PGE1 to cultured cells (3.3 or 33 microM) elicited an apparent increase in both the open probability (Po; ranging from 1.2-23 fold), and the mean open time (5-6 fold) of the KCa channel at membrane potentials of +90 mV and +110 mV. PGE1-induced alterations in KCa channel activity were also observed in freshly isolated corporal myocytes. In the whole cell-recording mode, statistically significant, Charybdotoxin-sensitive (100 nM) 2-3 fold increases in the outward K+ currents were observed in both cultured and freshly isolated corporal myocytes. The presence of a PKA inhibitor (fragment 6-22 amide; 10 microM) in the pipette tip was also associated with a nearly complete ablation of the observed PGE1-induced whole cell K+ currents. Taken together, these data confirm and extend our previous observations, and indicate that PGE1-induced relaxation of human corporal smooth muscle is related, at least in part, to activation of the KCa channel subtype resulting in cellular hyperpolarization.
Lee
S W
SW
Department of Urology, Sungkyunkwan University, College of Medicine, Seoul, Korea.
Wang
H Z
HZ
Zhao
W
W
Ney
P
P
Brink
P R
PR
Christ
G J
GJ
D000527:Alprostadil / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D004553:Electric Conductivity; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*
D015221:Potassium Channels; D018999:Charybdotoxin; D000527:Alprostadil; D002118:Calcium