Diabetes‐related alterations in second messenger regulation of potassium channel activity in corporal smooth muscle cells

Abstract

Corporal smooth muscle (CSM) relaxation mediates penile erection, and second messenger activation of the KCa and KATP channel subtypes plays a major role in this process. The goal of this study was to evaluate the potential role of altered second messenger activated hyperpolarizing K+ currents in CSM to diabetes (DM)‐related erectile dysfunction (ED). Corporal tissue was excised from the STZ‐DM rats following 2 months of DM. Whole cell currents were recorded from short‐term cultured CSM cells of DM and age‐matched control (AMC) rats; in the absence and presence of either cAMP (prostaglandin E1 (PGE1; 10 uM) or 8‐Br‐cAMP (1 mM)) or cGMP (sodium nitroprusside (SNP; 10 uM) or 8‐Br‐cGMP (1 mM)) activation. Holding potential was −70 mV, with I‐V curves constructed in 10 mV increments from −60 to +100 mV. Resting potentials were lower in DM (−44 ± 1.3 mV; n=40) than AMC (−56 ± 1.4 mV; n=40) (p<0.05). Outward whole cell K+ currents were reduced in DM (206 ± 11 pA; n=40) relative to AMC (321 ± 16 pA; n=40) (p<0.05). K+ currents induced by cGMP, SNP, cAMP and PGE1 were significantly diminished in DM relative to AMC. IBTX (100 nM) decreased cGMP‐activated K+ currents more than glibenclamide (GLIB; 10 uM) in AMC rats, but less than GLIB in DM rats. The data suggest that cGMP and cAMP‐mediated K+ currents are decreased in DM rats, and that altered regulation of the KCa and KATP channel subtypes might contribute to DM‐related ED in rats.