SIGNAL-TRANSDUCTION IN CAVERNOUS SMOOTH-MUSCLE

Knowledge of intracellular signal propagation in smooth-muscle tone re gulation is of major importance to the understanding of both the physi ology of erection and the pathophysiology of erectile dysfunction and the development of new and selective pharmacological agents in the tre atment of erectile dysfunction. Cavernous smooth-muscle tone depends h eavily on the amount of intracellular free Ca2+. In the resting state the sarcoplasmic free Ca2+ amounts to about 120-270 nM, whereas in the extracellular fluid the Ca2+ level is in the range of 1.5-2 mM. Elect romechanical and pharmacomechanical coupling induces an increase in th e levels of free sarcoplasmic Ca2+ by a factor of 2-3 to 550-700 nM th at triggers myosin phosphorylation and subsequent smooth muscle contra ction. In this case, modulation of membrane-bound ion channels and reg ulation of the intracellular second-messenger system are attractive an d feasible targets for pharmacological intervention. Besides the amoun t of free sarcoplasmic Ca2+, smooth-muscle tone is also modulated by t he regulation of Ca2+ sensitivity (''Ca-sensitization'') and Ca2+-inde pendent contraction processes.