Tonic and phasic GABAergic currents in premotor cardiac vagal neurons in the nucleus ambiguus

Abstract

GABA is a major inhibitory neurotransmitter which activates postsynaptic GABAA receptors in fast synaptic neurotransmission. In addition, GABA can escape, or spillover, from the synaptic cleft and activates receptors distant from the synapse. The current elicited from this leakage of GABA from the synapse is thought to cause a persistent or ‘tonic’ activation of GABAA receptors, resulting in a maintained hyperpolarizing current. Recent work has suggested the GABAA receptors responsible for the phasic and tonic currents have different pharmacological properties. This study examined the role of phasic and tonic GABAergic currents in cardiac vagal neurons (CVNs). CVNs were identified in-vitro by the presence of a retrograde fluorescent tracer and GABAergic synaptic events were recorded using patch clamp techniques. In current clamp configuration, gabazine blocked fast GABAergic neurotransmission, but did not significantly depolarize CVNs. However picrotoxin not only blocked fast inhibitory neurotransmission but also evoked a steady depolarization that often lead to spontaneous firing of CVNs. In voltage clamp configuration gabazine blocked fast GABAergic synaptic events, did not alter the holding current in CVNs, whereas picrotoxin additionally elicited a steady depolarizing decrease in holding current. This work demonstrates there are at least two types of GABAergic receptors in cardiac vagal neurons; gabazine sensitive GABAergic receptors involved in fast inhibitory neurotransmission, and a persistent picrotoxin (but not gabazine) sensitive current that plays an important role in determining the excitatory state of CVNs. Supported by NIH grants HL59895 and 72006 to D.M.