Figure 3. Penile smooth muscle contraction — the flaccid state.

a | Ca²⁺ influx into cells is regulated by noradrenaline signalling and levels of inositol-1,4,5-trisphosphate (Ins(1,4,5)P₃, which is produced from phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P₂) by phospholipase C) in the cells; increased intracellular Ca²⁺ binds to calmodulin, facilitating the formation of the calmodulin–myosin light chain kinase (MLCK) complex. This leads to the phosphorylation of MLC, resulting in smooth muscle contraction and a flaccid penis. Noradrenaline signalling also inhibits adenylyl cyclase and modulates the RHO-associated protein kinase (ROCK) pathway, which increases the sensitivity of MLC to Ca²⁺, a process negatively regulated by testosterone. Endothelins and prostaglandins from the endothelium also trigger an increase in intracellular Ca²⁺ to promote smooth muscle contraction. b | When the smooth muscle is contracted, inflow of blood through the cavernous artery is minimal, and blood outflows freely through the subtunical venular plexus. ER, endoplasmic reticulum; MLCP, myosin light chain phosphatase.