Comparative studies of the maxi-K (KCa) channel in freshly isolated myocytes of human and rat corpora

Abstract

Patch clamp techniques in freshly isolated myocytes from human corpora have documented that the large conductance calcium-sensitive K channel (K Ca ) subtype represents an important convergence point for the modulation of corporal smooth muscle tone, and therefore, erectile capacity. Other recent studies indicate a similar role for the K Ca channel in the modulation of smooth muscle tone in the rat penis. Therefore, the explicit aim of this investigation was to evaluate and compare the characteristics of the K Ca channel subtype present in freshly isolated myocytes from rat and human corpora. In short, myocytes isolated from rat and human corpora retain their characteristic morphology and contractility in vitro, as evidenced by light microscopic studies of their respective responses to activation of the a 1 -adrenergic receptor subtype by phenylephrine (PE). Large conductance K currents commensurate with the presence of the K Ca channel were readily apparent in myocytes from both preparations. I ± V curves constructed from cell-attached patches utilizing symmetric KCl solutions revealed the presence of a single channel slope conductance of % 200 pS for both rat and human myocytes. 1 mM TEA applied in the bath solution reversibly diminished whole cell outward K currents by % 50%, and also blocked the unitary K Ca channel activity observed in the outside-out patch mode. Addition of 2 mM 8-bromocAMP elicited a TEA-sensitive (1 mM) % 2 ± 3 fold increase in the magnitude of the whole cell outward K currents in rat myocytes. Taken together, these data con®rm and extend previous observations and provide strong evidence that the rat corporal smooth muscle K Ca channel has many similarities to its counterpart in the human penis.

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

“…[29][30][31] However, in the present investigation, the blockade of K Ca channels (both high Maxi-K and low-conductance K Ca ), with charybdotoxin and apamin, respectively, and the K ATP channels by glibenclamide did not modify significantly the F 3-5 -induced relaxation. These findings suggest that the relaxation effect of F 3-5 is unrelated to Ca 2 þ -activated, ATP-sensitive and voltage-dependent K þ channels.…”

Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel

“…20 Two isoforms of the channel, that is, the calcium-activated channels (K ca ) and adenosine triphosphate-sensitive channel (K ATP ), are the main modulators of the tone of the erectile tissue. 11 At least, injections of the K ATP -channel openers cromakalim and pinacidil in rabbit corpus cavernosum leads to relaxation, 8 intracavernosal injections of pinacidil, nicorandil, and lemakalim induces erection in cats, monkeys, and humans.…”

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…The activity of this channel is increased after cellular activation of either the cAMP pathway by 8-bromo-cAMP or PGE 1 (Lee et al, 1999a) or the cGMP pathway by 8-bromo-cGMP (Wang et al, 2000). It seems clear that the two most physiologically relevant endogenous second-messenger pathways act to modulate corporal smooth muscle tone (i.e., elicit relax-ERECTILE MECHANISMS AND ED TREATMENT ation), at least in part, via activation of the BK Ca channel subtype.…”

“…The BK Ca Channel. The BK Ca channel has been well characterized in both human and rat corporal smooth muscle (Wang et al, 2000;Archer, 2002). BK Ca channels are formed by two subunits: a pore-forming ␣-subunit and a modulatory transmembrane ␤-subunit.…”