Neurohumoral regulation of excitation-contraction coupling in ventricular myocytes from cardiomyopathic hamsters.
OBJECTIVE
The aim was to evaluate the regulation of contractility by autonomic stimulation in the necrotic stage of cardiomyopathy in male Syrian hamsters.


METHODS
The electrical and contractile activity of isolated intracellularly stimulated ventricular myocytes has been recorded and dose-response curves to [Ca2+]o, and to beta adrenergic, alpha adrenergic, and muscarinic agonists and antagonists were examined.


METHODS
Ventricular cardiomyocytes were isolated by enzymatic dissociation of hearts from 90 to 120 day old cardiomyopathic hamsters CHF 147 and from age matched non-myopathic controls: CHF 148 or golden hamsters.


RESULTS
The membrane potential was recorded by suction (patch) electrodes. The contractile activity was recorded by a video system as the shortenings of the myocytes. The contractile response (EC50) to beta adrenergic stimulation (isoprenaline) showed a bimodal distribution: 60% of the myopathic myocytes responded like the controls, while in the remaining 40% the sensitivity was significantly decreased. The electrical activity and beta adrenergic receptor density were not different from the controls. The alpha adrenergic stimulation (by phenylephrine) was enhanced, while response to the muscarinic agonist carbachol (in the presence of isoprenaline) was attenuated in the myopathic cells. Sensitivity to [Ca2+]o was unchanged.


CONCLUSIONS
Profound changes occur in the contractile response of myocytes from cardio-myopathic hamster to stimulation by mediators of the autonomic nervous system, which at this necrotic stage are not related to any significant changes in basal contractile response to [Ca2+]o, to the electrical activity, or to the number of beta adrenergic receptors.
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
M
M
Horackova
A
A
Beresewicz
G
G
Rowden
M
M
Wilkinson
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002462:Cell Membrane / Q000737:chemistry; D006224:Cricetinae; D004594:Electrophysiology; D006321:Heart / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D013268:Stimulation, Chemical; D014741:Video Recording
D018377:Neurotransmitter Agents; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D002217:Carbachol; D007545:Isoproterenol