Modulation of Transient and Persistent Inward Currents by Activation of Protein Kinase C in Spinal Ventral Neurons of the Neonatal Rat

Abstract

Neuronal excitability can be regulated through modulation of voltage threshold ( Vth). Previous studies suggested that this modulation could be mediated by modulation of transient sodium currents ( IT) and/or persistent inward current (PIC). Modulation of ITand PIC through activation of protein kinase C (PKC) has previously been described as a mechanism controlling neuronal excitability. We investigated modulation of ITand PIC by PKC in neonatal rat spinal ventral neurons. In whole cell voltage clamp, activation of PKC by application of 1-oleoyl-2-acetyl-sn-glycerol (OAG, 10–30 μM) resulted in 1) a reduction of ITamplitude by 33% accompanied an increase in half-width and a decrease in the maximal rise and decay rates of the IT; 2) a reduction of PIC amplitude by 49%, with a depolarization of PIC onset by 4.5 mV. Activation of PKC caused varied effects on Vthfor eliciting IT, with an unchanged Vthor depolarized Vthbeing the most common effects. In current-clamp recordings, PKC activation produced a small but significant depolarization (2.0 mV) of Vthfor action potential generation with an increase in half-width and a decrease in amplitude and the maximal rise and decay rates of action potentials. Inclusion of PKCI19–36(10–30 μM), a PKC inhibitor, in the recording pipette could block the OAG effects on ITand PIC. The ability of serotonin to hyperpolarize Vthwas not altered by PKC activation or inhibition. This study demonstrates that activation of PKC decreases the excitability of spinal ventral neurons and that Vthcan be modulated by multiple mechanisms.