A Model for Pleiotropic Muscarinic Potentiation of Fast Synaptic Transmission

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Abstract
The predominant form of muscarinic excitation in the forebrain and in sympathetic ganglia arises from m1 receptors coupled to the Gq/11signal transduction pathway. Functional components of this system have been most completely mapped in frog sympathetic B neurons. Presynaptic stimulation of the B neuron produces a dual-component muscarinic excitatory postsynaptic potential (EPSP) mediated by suppression of voltage-dependent M-type K+channels and activation of a voltage-insensitive cation current. Evidence from mammalian systems suggests that the cation current is mediated by cyclic GMP-gated channels. This paper describes the use of a computational model to analyze the consequences of pleiotropic muscarinic signaling for synaptic integration. The results show that the resting potential of B neurons is a logarithmic function of the leak conductance over a broad range of experimentally observable conditions. Small increases (+leak can substitute for the cation conductance in producing excitatory muscarinic actions. The results are discussed in terms of their implications for synaptic integration in sympathetic ganglia and other circuits.