Ion channels and gap junctions: Their role in erectile physiology, dysfunction, and future therapy

A flurry of research and clinical activity during this past decade has docu mented that the tonicity and synchronicity of the corporal smooth muscle ce lls of the penis are major determinants of erectile capacity and function. Specifically, the effects of diverse and bifurcating intracellular signal t ransduction pathways on the activity of nonjunctional ion channels such as potassium (K+), calcium (Ca2+), and chloride (Cl-) govern the former, where as intercellular communication through gap junctions provides the anatomic substrate for the latter. Recent studies at the tissue, cellular, subcellul ar, and molecular levels have verified this supposition and provided import ant insight into how subtle alterations in the balance between contraction and relaxation of the corporal smooth muscle cells can predispose a man to erectile failure. This report reviews the available information concerning the participation of gap junctions and K+, Ca2+, and Cl- channels in the er ectile process and describes their importance as potential molecular target s for the future therapy of erectile dysfunction (ED). It is argued that a major goal should now be to proceed on at least two fronts simultaneously: (1) to capitalize on these new mechanistic insights by developing novel tre atments for ED centered on the modulation of ion channel activity; and (2) simultaneously to take advantage of the unique therapeutic opportunities af forded by the presence and ubiquitous distribution of gap junction channels in the human corpora, One strategy that fulfils both criteria will be brie fly reviewed, that is, gene therapy with the maxi-K+ channel subtype.