AN ANALYSIS OF THE MAXI-K+ (K-CA) CHANNEL IN CULTURED HUMAN CORPORAL SMOOTH-MUSCLE CELLS

Previous studies have demonstrated that cultured corporal smooth muscle cells have prominent outward K currents composed of several different K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteristics of the most predominant of these channel subtypes, the Maxi-K+ (K-Ca) channel, and (2) to compare K-Ca channel behavior in cultured corporal smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivided into two broad diagnostic categories: Group 1: 4 patients without evidence of organic disease of the corpus cavernosum, 3 of whom had documented erections; and Group 2: 4 patients with organic erectile dysfunction. Consistent with previous observations, 3 different K channel subtypes were detected in both patient populations, with corresponding conductances of 180, 100 and 40 pS, respectively. The approximate to 183 pS channel was identified as the K-Ca channel based on its selective permeability to K+ and the fact that its open probability was modulated by both membrane potential and intracellular calcium levels. Specifically, the relative permeability of the 183 pS K-Ca channel to K+, Rb and NH4+ was 1.00:0.64:0.46. The channel was virtually impermeable to Na+ and Li+ (relative permeability <0.02). In addition, the K-Ca channel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacological studies using the K channel blocker tetraethylammonium ion (TEA) revealed that the sensitivity of K-Ca channels to TEA inhibition (as judged by the [TEA] required to block one-half of the outward whole cell current induced by a 90 mV depolarizing pulse) in cells from Group 1 patients was 1.05 +/- 0.22 mM. (n = 10 cells), while in sharp contrast the observed value for cells from Group 2 patients was 12.7 +/- 3.8 (n = 9 cells). The difference between the two groups was highly significant. These observations confirm and extend our previous studies to suggest that the K-Ca channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/regulation of K-Ca channels may be an important feature of organic erectile dysfunction. As such, altered K-Ca channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, possibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone.