K channels as molecular targets for the treatment of erectile dysfunction

Abstract

K channels appear to provide an ideal molecular target for regulating corporal smooth muscle cell tone and therefore erectile capacity. They do so by virtue of the central role they play in integrating cellular signals and furthermore, because alterations in their activity are commensurate with the modulation, but not ablation, of smooth muscle cell tone. Since both tissue-specific expression and tissue-specific function are characteristics of the multisubunit complexes that comprise the maxi-K and KATP channel subtypes, significant potential exists for developing novel chemicals that can selectively activate these channels in target tissues. Moreover, the quiescence of these channels during flaccidity and the robust increase in their activity levels during endogenous stimulation bode well for their potential as erectogenic agents. Finally, the ability of intercellular communication through gap junctions to efficiently spread K channel-mediated hyperpolarizing signals throughout the corporal smooth muscle cell network implies that low-efficiency gene transfer techniques will provide a unique circumstance in which high-efficacy treatments can be locally delivered to the penis, thus further minimizing the potential for systemic side effects.