title: Endothelin-1 receptor blockade prevented the electrophysiological dysfunction in cardiac myocytes of streptozotocin-induced diabetic rats.
abstract: Diabetes mellitus is complicated with the development of cardiac contractile dysfunction and electrical instability, which contributes to high morbidity and mortality in diabetic patients. This study examined the possible roles of enhanced endothelin-1 (ET-1) on diabetes-induced alterations in ventricular myocyte electrophysiology. Type 1 diabetic rats were induced by single dose injection of streptozotocin (STZ) and treated with or without ET-1 receptor antagonist bosentan for 8 wk before myocyte isolation. Action potential, outward K+ currents, and inward Ca2+ currents in ventricular myocytes were recorded using whole-cell patch clamp technique. STZ-injected rats exhibited hyperglycemia, reduced body weight gain, and elevated plasma ET-1 concentration, indicative of diabetes induction. Ventricular myocytes isolated from diabetic rats exhibited prolonged action potential and reduced all three types of outward K+ currents. Resting membrane potential, height of action potential, and L-type Ca2+ current were not altered in diabetic myocytes. In vivo chronic treatment of diabetic rats with bosentan significantly augmented K+ currents and reversed action potential prolongation in ventricular myocytes. On the other hand, bosentan treatment had no detectable effect on the electrophysiological properties in control myocytes. In addition, bosentan had no effect on Ltype Ca2+ currents in both control and diabetic myocytes. Our data suggest that altered electrophysiological properties in ventricular myocytes were largely resulted from augmented ET-1 system in diabetic animals.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Ding
authors.forename: Ruijiao
authors.initials: R
authors.lastname: Zou
authors.forename: Robert L
authors.initials: RL
authors.lastname: Judd
authors.forename: Juming
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D000077300:Bosentan; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D065130:Endothelin A Receptor Antagonists; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D044022:Receptor, Endothelin A / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D020746:Calcium Channels, L-Type; D065130:Endothelin A Receptor Antagonists; D015221:Potassium Channels; D044022:Receptor, Endothelin A; D013449:Sulfonamides; D000077300:Bosentan