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Augmentation of M‐Current and Increased Synaptic Efficacy at Intrinsic Cardiac Neurons Contributes to an Enhanced Cardiac Responsiveness to Vagal Nerve Stimulation in the Infarcted Porcine Heart
Author(s) -
Tompkins John D.,
Buckley Una,
Salavatian Siamak,
Shivkumar Kalyanam,
Ardell Jeffrey
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.596.3
Subject(s) - hexamethonium , stimulation , afterhyperpolarization , medicine , excitatory postsynaptic potential , cholinergic , cardiology , neuroscience , endocrinology , electrophysiology , biology , inhibitory postsynaptic potential
Imbalances to autonomic regulation of cardiac function contribute to risk for arrhythmia after myocardial infarction (MI). We tested the hearts responsiveness to vagal nerve stimulation (VNS), 8 wks after MI, to determine if parasympathetic control of the heart is altered in MI pigs. A significantly greater bradycardic response was elicited in MI animals during 20Hz stimulation. Intracellular voltage recordings from whole‐mount preparations of intrinsic cardiac neurons (ICNs) were subsequently used to assess whether alterations in neuronal membrane properties or synaptic transmission underlie the observed increase in responsiveness to VNS in MI animals. General membrane properties (resting membrane potential, input resistance, action potential amplitude/duration, afterhyperpolarization amplitude/duration) of ICNs from control and MI pigs were not different, but ICN excitability was significantly depressed in MI pigs. Testing synaptic efficacy revealed a greater proportion of strong (high AP probability) vs weak synapses (low AP probability) in MI animals. Tetanic stimulation (20Hz) of interganglionic nerve bundles elicited slow excitatory postsynaptic potentials (sEPSPs) in a significantly greater subset of MI ICNs (10/22) vs controls (4/26). The sEPSP persisted in hexamethonium (500uM) but was blocked by atropine (1uM), indicating mediation by cholinergic inhibition of M‐current. Application of 1mM Ba 2+ increased excitability of ICNs from both control and MI animals further supporting a role for M‐current in the regulation of porcine ICN excitability. In hexamethonium, the amplitude of the sEPSP was significantly greater in MI ICNs. In conclusion, we identify a important role of M‐current in the regulation of the excitability of porcine ICNs, and demonstrate enhanced membrane depolarization of ICNs from MI animals after presynaptic stimulation due, in part, to greater inhibition of I M during tetanic nerve stimulation which may underlie the enhanced sensitivity to VNS in MI pigs. Support or Funding Information This work was supported in part by NIH grant OT2OD023848. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .