Physiological roles and properties of potassium channels in corporal smooth muscle.

Decreased penile vascular resistance induced by corporal smooth muscle relaxation is the most important step in penile erection. The heightened tone of the corporal smooth muscles is considered a major cause in impotence. Modulation of corporal smooth muscle tone is a complex process requiring the integration of a host of intracellular events and extracellular signals. In intracellular events of corporal smooth muscle cell, the potassium channels and calcium channels play a major role. Functionally, potassium channels are important regulators of smooth muscle membrane potential in response to depolarizing stimuli and they counteract calcium channels. Potassium channels have been shown to play a fundamental role in both the physiologic and pathophysiologic regulation of smooth muscle tone in diverse tissues. Among the several subtypes of potassium channels, the calcium-sensitive (K(Ca)) or maxi-K potassium channel subtypes are thought to be the most physiologically relevant in human corporal smooth muscle. Because of the physiological role of maxi-K channels in human corporal smooth muscles, we investigated the maxi-K channels for the genetic therapy of erectile dysfunction. These data indicate that naked hSlo DNA of maxi-K channels is quite easily incorporated into corporal smooth muscle and expression of the maxi-K hSlo cDNA appeared to be sustained for 1-4 months postinjection. These results show the possibility of a similar genetic strategy of potassium channels in humans.