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

Dai Y, Jordan LM, Fedirchuk B. Modulation of transient and persistent inward currents by activation of protein kinase C in spinal ventral neurons of the neonatal rat. J Neurophysiol 101: 112-128, 2009. First published October 22, 2008; doi:10.1152/jn.01373.2007. Neuronal excitability can be regulated through modulation of voltage threshold (V-th). Previous studies suggested that this modulation could be mediated by modulation of transient sodium currents (I-T) and/or persistent inward current (PIC). Modulation of I-T and PIC through activation of protein kinase C (PKC) has previously been described as a mechanism controlling neuronal excitability. We investigated modulation of I-T and 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 mu M) resulted in 1) a reduction of I-T amplitude by 33% accompanied an increase in half-width and a decrease in the maximal rise and decay rates of the I-T; 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 V-th for eliciting I-T, with an unchanged V-th or depolarized V-th being the most common effects. In current-clamp recordings, PKC activation produced a small but significant depolarization (2.0 mV) of V-th for 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 mu M), a PKC inhibitor, in the recording pipette could block the OAG effects on I-T and PIC. The ability of serotonin to hyperpolarize V-th was not altered by PKC activation or inhibition. This study demonstrates that activation of PKC decreases the excitability of spinal ventral neurons and that V-th can be modulated by multiple mechanisms.