A 19-year-old man presents to a psychiatrist for a follow-up appointment for generalized anxiety disorder (GAD) and major depressive disorder (MDD). Medical history is otherwise unremarkable. His GAD and MDD were unresponsive to adequate trials of 2 different selective serotonin reuptake inhibitors (SSRIs), so the psychiatrist decided to start a serotonin-norepinephrine reuptake inhibitor (SNRI) at the previous visit. Today, he reports improvement in GAD and MDD symptoms, but he states he is having trouble achieving erections. He did not experience this side effect with either of the SSRIs. Review of systems is negative. Physical examination is normal.
Which of the following changes in intracellular ion concentration in smooth muscle is most likely leading to erectile dysfunction in this patient?
D) Increased [Ca2+]
Smooth muscle contraction causes vasoconstriction, which opposes erection. During tumescence, nitric oxide increases guanocine3,5-cyclic monophosphate (cyclic GMP). cGMP causes smooth muscle relaxation, which in turn causes vasodilation of blood vessels in the corpus cavernosum, causing erection. Erectile dysfunction is commonly experienced with SSRI’s, but it can also occur with SNRIs. Norepinephrine increases intracellular calcium concentration in smooth muscle, causing smooth muscle contraction that opposes erection.
Answer Choice A: Decreased [Ca2+], is incorrect. This occurs in the normal physiology of an erection, not erectile dysfunction.
Answer Choice B: Decreased [Mg2+], is incorrect. This could cause excitoxicity in neurons but is not involved in smooth muscle contraction.
Answer Choice C: Decreased [Na+], is incorrect. Opening of L-type calcium channels, not sodium channels, triggers depolarization of smooth muscle cells.
Answer Choice E: Increased [Na+], is incorrect. Opening of L-type calcium channels, not sodium channels, triggers depolarization of smooth muscle cells. Increased intracellular sodium occurs in cardiomyocyte depolarization.
Key Learning Point
In male erection physiology, a decrease in intracellular calcium causes smooth muscle relaxation, leading to vasodilation. Norepinephrine interferes with normal erection physiology via increased intracellular calcium concentration -> smooth muscle contraction.
