title: Heart failure-induced changes of voltage-gated Ca2+ channels and cell excitability in rat cardiac postganglionic neurons.
abstract: Chronic heart failure (CHF) is characterized by decreased cardiac parasympathetic and increased cardiac sympathetic nerve activity. This autonomic imbalance increases the risk of arrhythmias and sudden death in patients with CHF. We hypothesized that the molecular and cellular alterations of cardiac postganglionic parasympathetic (CPP) neurons located in the intracardiac ganglia and sympathetic (CPS) neurons located in the stellate ganglia (SG) possibly link to the cardiac autonomic imbalance in CHF. Rat CHF was induced by left coronary artery ligation. Single-cell real-time PCR and immunofluorescent data showed that L (Ca(v)1.2 and Ca(v)1.3), P/Q (Ca(v)2.1), N (Ca(v)2.2), and R (Ca(v)2.3) types of Ca2+ channels were expressed in CPP and CPS neurons, but CHF decreased the mRNA and protein expression of only the N-type Ca2+ channels in CPP neurons, and it did not affect mRNA and protein expression of all Ca2+ channel subtypes in the CPS neurons. Patch-clamp recording confirmed that CHF reduced N-type Ca2+ currents and cell excitability in the CPP neurons and enhanced N-type Ca2+ currents and cell excitability in the CPS neurons. N-type Ca2+ channel blocker (1 μM ω-conotoxin GVIA) lowered Ca2+ currents and cell excitability in the CPP and CPS neurons from sham-operated and CHF rats. These results suggest that CHF reduces the N-type Ca2+ channel currents and cell excitability in the CPP neurons and enhances the N-type Ca2+ currents and cell excitability in the CPS neurons, which may contribute to the cardiac autonomic imbalance in CHF.
authors.affiliation: Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, Nebraska;
authors.forename: Huiyin
authors.initials: H
authors.lastname: Tu
authors.forename: Jinxu
authors.initials: J
authors.lastname: Liu
authors.forename: Dongze
authors.initials: D
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Kaushik P
authors.initials: KP
authors.lastname: Patel
authors.forename: Kurtis G
authors.initials: KG
authors.lastname: Cornish
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
authors.forename: Robert L
authors.initials: RL
authors.lastname: Muelleman
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002478:Cells, Cultured; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013233:Stellate Ganglion / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type
keywords: action potential; autonomic dysfunction; cardiac ganglia; ion channels
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