Contribution of the Na<sup>+</sup>/K<sup>+</sup> Pump to Rhythmic Bursting, Explored with Modeling and Dynamic Clamp Analyses

Acetylcholine excites many neuronal types by binding to postsynaptic m1-muscarinic receptors that signal to ion channels through the Gq/11 protein. To investigate the functional significance of this metabotropic pathway in sympathetic ganglia, we studied how muscarinic excitation modulated the integration of virtual nicotinic excitatory postsynaptic potentials (EPSPs) created in dissociated bullfrog B-type sympathetic neurons with the dynamic-clamp technique. Muscarine (1 μM) strengthened the impact of virtual synapses by reducing the artificial nicotinic conductance required to reach the postsynaptic firing threshold from 20.9 ± 5.4 to 13.1 ± 3.1 nS. Consequently, postganglionic action potential output increased by 4–215% when driven by different patterns of virtual presynaptic activity that were chosen to reflect the range of physiological firing rates and convergence levels seen in amphibian and mammalian sympathetic ganglia. In addition to inhibiting the M-type K+ conductance, muscarine activated a leak conductance in three of 37 cells. When this leak conductance was reproduced with the dynamic clamp, it also acted to strengthen virtual nicotinic synapses and enhance postganglionic spike output. Combining pharmacological M-conductance suppression with virtual leak activation, at resting potentials between −50 and −55 mV, produced synergistic strengthening of nicotinic synapses and an increase in the integrated postganglionic spike output. Together, these results reveal how muscarinic activation of a branched metabotropic pathway can enhance integration of fast EPSPs by modulating their effective strength. The results also support the hypothesis that muscarinic synapses permit faster and more accurate feedback control of autonomic behaviors by generating gain through synaptic amplification in sympathetic ganglia.

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Contribution of the Na+/K+ Pump to Rhythmic Bursting, Explored with Modeling and Dynamic Clamp Analyses

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