Participation of a persistent sodium current and calcium-activated nonspecific cationic current to burst generation in trigeminal principal sensory neurons

The properties of neurons participating in masticatory rhythmogenesis are not clearly understood. Neurons within the dorsal trigeminal principal sensory nucleus (dPrV) are potential candidates as components of the masticatory central pattern generator (CPG). The present study examines in detail the ionic mechanisms controlling burst generation in dPrV neurons in rat (postnatal day 8-12) brain stem slices using whole cell and perforated patch-clamp methods. Nominal extracellular Ca2+ concentration transformed tonic discharge in response to a maintained step pulse of current into rhythmical bursting in 38% of nonbursting neurons. This change in discharge mode was suppressed by riluzole, a persistent Na+ current (I-NaP) antagonist. Veratridine, which suppresses the Na+ channel inactivation mechanism, induced rhythmical bursting in nonbursting neurons in normal artificial cerebrospinal fluid, suggesting that I-NaP contributes to burst generation. Nominal extracellular Ca2+ exposed a prominent afterdepolarizing potential (ADP) following a single spike induced by a 3-ms current pulse, which was suppressed, but not completely blocked, by riluzole. Application of BAPTA, a Ca2+ chelator, intracellularly, or flufenamic acid, a Ca2+-activated nonspecific cationic channel (I-CAN) antagonist, extracellularly to the bath, suppressed rhythmical bursting and the postspike ADP. Application of drugs to alter Ca2+ release from endoplasmic reticulum also suppressed bursting. Finally, voltage-clamp methods demonstrated that nominal Ca2+ facilitated I-NaP and induced I-CAN. These data demonstrate for the first time that the previously observed induction in dPrV neurons of rhythmical bursting in nominal Ca2+ is mediated by enhancement of I-NaP and onset of I-CAN, which are dependent on intracellular Ca2+