Post-Ischemic Spine Recovery Depends on Perfusion Level

Inflammatory molecules sensitize peripheral nociceptors, making them responsive to innocuous stimuli. Sensitization is mediated by protein kinase A (PKA), but the ion channels involved are not known. PKA increases expression of voltage-gated sodium channels, but knock-out of these channels does not eliminate inflammation-induced sensitization. PKA also decreases potassium currents, but the percentage change in current was reportedly small. Nuwer et al. noted, however, that the latter studies were conducted in sodium-free medium, and thereforecouldnotidentifyeffectsonsodiumactivated potassium (KNa) channels, which are highly expressed in nociceptors. With physiological sodium concentrations, a PKA activator caused a 50% decrease in potassium current in cultured rat dorsal root ganglion neurons. PKA did not alter gating of KNa channels but, rather, reduced levels of KNa subunits in the plasma membrane. Furthermore, knock-down of these subunits increased the number of spikes elicited by current injection, as does activation of PKA.