Encoding properties induced by a persistent voltage-gated muscarinic sodium current in rabbit sympathetic neurones

A time- and voltage-dependent Na+-selective current termed INa,M is activated by muscarinic agonists or splanchnic nerve stimulation in sympathetic neurones of rabbit coeliac and superior mesenteric ganglia. The firing patterns induced by INa,M were investigated in patch-clamped neurones within intact ganglia, and compared with those generated by a neuronal model including INa,M.INa,M was characterized by voltage-dependent low-threshold activation and high-threshold inactivation functions. The overlapping functions produced a persistent U-shaped current between −100 and −20 mV, which peaked at the cell resting potential. The activation and inactivation kinetics were fitted to single exponentials with time constants of ≈100 and 400 ms, respectively.Activating INa,M with muscarinic agonists or nerve stimulation depolarized and fired the neurones. The depolarization was paralleled by an apparent increase in input membrane resistance. The model showed that this paradox resulted from the turning off of INa,M during resistance tests, which also accounted for the all-or-none slow hyperpolarizing responses to current pulses.INa,M gave the neurones an N-shaped I-V relationship capable of producing complex firing patterns. Under given conditions, carbachol-treated neurones could either fire regularly or remain silent at ≈-80 mV, i.e. they displayed bistability. Transitions from one state to the other were triggered with short current pulses. The transitions resulted from the turning on and off of INa,M.Firing reduced INa,M, an effect abolished by blocking Ca2+ channels or adding BAPTA (40 mM) to the pipette. The Ca2+-related negative regulation of INa,M may have mediated endogenous bursting activity. Burst firing was generated by the model upon introducing Ca2+ regulation of INa,M.The results demonstrate that INa,M gives prevertebral sympathetic neurones a wide repertoire of firing patterns: pacemaker-like properties, bistability and burst firing capability. They suggest that the INa,M-related encoding properties may provide sympathetic neurotransmission with new potentialities