Process Penile Erection

SMOOTH MUSCLE CONTRACTION AND RELAXATION IS REGULATED BY Ca2+-INDUCED MYOSIN PHOSPHORYLATION AND DEPHOSPHORYLATION.

The primary stimulus for corporal smooth muscle contraction (penile flaccidity) again depends on the concentration of intracellular calcium. When the intracellular concentra-tion of calcium increases to 10.5 mol/L, Ca2+ forms an active complex with the calcium-

binding protein calmodulin. The Ca2+–calmodulin complex then activates a Ca2+–cal-modulin-dependent myosin light chain kinase (MLCK). The activated MLCK phospho-rylates the regulatory MLC20, leading to smooth muscle contraction. A decrease in intracellular calcium to basal levels (<10.5 mol/L) inactivates MLCK and allows for dephosphorylation of the MLC20 by a Ca2+-independent MLC phosphatase, lowering the actin-activated ATPase activity of myosin. This allows for the myosin to detach from actin and leads to corporal smooth muscle relaxation (penile erection). It has been demonstrated that activation of both ET-1 and α1-adrenoreceptors leads to a transient 3-to 10-fold increase in intracellular calcium levels in corporal smooth muscle cells. Additional mechanisms by which cytoplasmic Ca2+ are reduced include cyclic adenosine monophosphate (cAMP) acting through protein kinase A (PKA) and cGMP acting via PKG or directly via activation of potassium channels that lead to cell mem-brane hyperpolarization. Hyperpolarization prevents the opening of voltage-dependent calcium channels.