The modulation of CA²⁺ sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle

Purpose: We examined the role of the modulation of Ca²⁺ sensitivity for regulating the contractility of corpus cavernosum smooth muscle. Materials and Methods: We applied simultaneous measurements of intracellular Ca²⁺ concentration and tension in fura-PE3 loaded intact strips and receptor coupled permeabilization by α-toxin. Results: In intact fura-PE3 loaded strips the tension induced by 10 μM. phenylephrine was significantly greater than that produced by depolarization with 118 mM. K⁺, although the extent of intracellular Ca²⁺ concentration elevations was similar. During sustained contraction induced by 10 μM. phenylephrine the application of 10 μM. Y-27632 (a Rho kinase inhibitor) induced relaxation with a slight decrease in intracellular Ca²⁺ concentration, while the application of 3 μM. GF109203X (a protein kinase C inhibitor) induced relaxation without changing intracellular Ca²⁺ concentration. In α-toxin permeabilized strips 10 μM. phenylephrine induced a larger increase in force at a constant intracellular Ca²⁺ concentration and produced a leftward shift in the intracellular Ca²⁺ concentration-tension relationship, a response that was partially inhibited by pretreatment with Y-27632 or GF109203X. Conclusions: These results indicate that in rabbit corpus cavernosum smooth muscle phenylephrine induces contraction not only by increasing intracellular Ca²⁺ concentration, but also by increasing Ca²⁺ sensitivity of the contractile apparatus in a Rho kinase and protein kinase C dependent manner. Antagonism of Ca²⁺ sensitization pathways in the corpus cavernosum smooth muscle represents an alternate target for the treatment of erectile dysfunction.