K+ channels and gap junctions in the modulation of corporal smooth muscle tone.
Changes in the contractile status (i.e., contraction and relaxation) of corporal and arterial smooth muscle cells (myocytes) govern the flow of blood to and from the penis and, thus, ultimately have a major impact on erectile capacity. As with many other smooth muscle cell types, corporal myocyte contractility is inextricably linked to ion channel activity. Corporal smooth muscle cells possess a rich repertoire of ion channels, including calcium, chloride and potassium channels, as well as gap junction (intercellular) channels. Among these, the K(ATP) (i.e., the metabolically regulated K(+) channel) and the K(Ca) (i.e., maxi-K or large conductance, calcium-sensitive K(+) channel) nonjunctional channel subtypes, as well as connexin43-derived gap junction (intercellular) channels, are thought to be particularly relevant to the control of corporal myocyte contractility. In fact, whereas K(+) channels are an important convergence point for modulating cellular function, gap junctions are a major conduit for ensuring coordinated cellular, and thus tissue, function. The evidence documenting the presence and physiological relevance of K(+) channels and gap junctions to human erectile physiology and function is reviewed. Finally, one potentially revolutionary therapeutic strategy that takes advantage of the important contribution of K(+) channels and gap junctions to erectile physiology is described: maxi-K ion channel (gene) therapy.
Christ
G J
GJ
Department of Urology, and Institute for Smooth Muscle Biology, Laboratory of Molecular and Integrative Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.