Abstract
Knowledge of intracellular signal propagation in smooth-muscle tone regulation is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction and the development of new and selective pharmacological agents in the treatment of erectile dysfunction. Cavernous smooth-muscle tone depends heavily 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. Electromechanical and pharmacomechanical coupling induces an increase in the levels of free sarcoplasmic Ca2+ by a factor of 2-3 to 550-700 nM that triggers myosin phosphorylation and subsequent smooth muscle contraction. In this case, modulation of membrane-bound ion channels and regulation of the intracellular second-messenger system are attractive and feasible targets for pharmacological intervention. Besides the amount of free sarcoplasmic Ca2+, smooth-muscle tone is also modulated by the regulation of Ca2+ sensitivity ("Ca-sensitization") and Ca(2+)-independent contraction processes.
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