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

Previous studies have demonstrated that cultured corporal smooth muscl e cells have prominent outward K currents composed of several differen t K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteris tics of the most predominant of these channel subtypes, the Maxi-K+ (K -Ca) channel, and (2) to compare K-Ca channel behavior in cultured cor poral smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivide d into two broad diagnostic categories: Group 1: 4 patients without ev idence of organic disease of the corpus cavernosum, 3 of whom had docu mented erections; and Group 2: 4 patients with organic erectile dysfun ction. Consistent with previous observations, 3 different K channel su btypes were detected in both patient populations, with corresponding c onductances of 180, 100 and 40 pS, respectively. The approximate to 18 3 pS channel was identified as the K-Ca channel based on its selective permeability to K+ and the fact that its open probability was modulat ed by both membrane potential and intracellular calcium levels. Specif ically, 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 chan nel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacologi cal studies using the K channel blocker tetraethylammonium ion (TEA) r evealed that the sensitivity of K-Ca channels to TEA inhibition (as ju dged 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 signifi cant. These observations confirm and extend our previous studies to su ggest that the K-Ca channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/reg ulation of K-Ca channels may be an important feature of organic erecti le dysfunction. As such, altered K-Ca channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, poss ibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone.