Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction.
Myocardial infarction (MI) is associated with remodeling of the heart and neurohumoral control systems. The objective of this study was to define time-dependent changes in intrinsic cardiac (IC) neuronal excitability, synaptic efficacy, and neurochemical modulation following MI. MI was produced in guinea pigs by ligation of the coronary artery and associated vein on the dorsal surface of the heart. Animals were recovered for 4, 7, 14, or 50 days. Intracellular voltage recordings were obtained in whole mounts of the cardiac neuronal plexus to determine passive and active neuronal properties of IC neurons. Immunohistochemical analysis demonstrated an immediate and persistent increase in the percentage of IC neurons immunoreactive for neuronal nitric oxide synthase. Examination of individual neuronal properties demonstrated that after hyperpolarizing potentials were significantly decreased in both amplitude and time course of recovery at 7 days post-MI. These parameters returned to control values by 50 days post-MI. Synaptic efficacy, as determined by the stimulation of axonal inputs, was enhanced at 7 days post-MI only. Neuronal excitability in absence of agonist challenge was unchanged following MI. Norepinephrine increased IC excitability to intracellular current injections, a response that was augmented post-MI. Angiotensin II potentiation of norepinephrine and bethanechol-induced excitability, evident in controls, was abolished post-MI. This study demonstrates that MI induces both persistent and transient changes in IC neuronal functions immediately following injury. Alterations in the IC neuronal network, which persist for weeks after the initial insult, may lead to alterations in autonomic signaling and cardiac control.
Department of Biology, Ithaca College, Ithaca, NY 14850, United States. Electronic address: jhardwick@ithaca.edu.
Jean C
JC
Hardwick
Department of Biology, Ithaca College, Ithaca, NY 14850, United States.
Shannon E
SE
Ryan
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Eric
E
Beaumont
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Jeffrey L
JL
Ardell
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
E Marie
EM
Southerland
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D018723:Bethanechol / Q000494:pharmacology; D002908:Chronic Disease; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013566:Sympathomimetics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D010277:Parasympathomimetics; D013566:Sympathomimetics; D014662:Vasoconstrictor Agents; D018723:Bethanechol; D000804:Angiotensin II; D052248:Nitric Oxide Synthase Type I; D009638:Norepinephrine
Angiotensin II; Bethanechol; Intrinsic cardiac nervous system; Myocardial infarction; Neuromodulation; Norepinephrine