title: Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia.
abstract: It was recently suggested that the antiarrhythmic effect of propranolol, a ss-adrenoceptor antagonist, on ischemic myocardium includes restoration of I(K1) current and Cx43 conductance; however, little is known whether effects on the transient outward current I(to) contribute. A model of myocardial infarction (MI) by ligating the left anterior descending coronary artery was established. Propranolol was given 1 h or daily for 3 months, whole-cell patch-clamp techniques were used to measure I(to). Kv4.2 and PKA levels were analyzed by Western blot and cAMP level was determined by radioimmunoassay. The results showed that propranolol decreased the incidence of arrhythmias induced by acute ischemia and mortality in 3 month MI rats. Propranolol restored the diminished I(to) density and Kv4.2 protein in MI hearts. In addition, neonatal cardiomyocyte pretreatment with propranolol or administrated after hypoxia can resume I(to) density. cAMP/PKA was enhanced in acute MI, the reason of decreased Kv4.2 expression. Treatment with propranolol prevented the increased cAMP/PKA in 1 h MI, whereas propranolol had little effect on decreased cAMP/PKA in 3 months MI. This study demonstrated that both short- and long-term propranolol administrations protect cardiomyocytes against arrhythmias and mortality caused by cardiac ischemia; the involvement of cAMP/PKA signal pathway in the regulation of propranolol on I(to) acted differently along with the ischemic progression.
authors.affiliation: Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Chao-Qian
authors.initials: CQ
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hong
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Yan-Xiu
authors.initials: YX
authors.lastname: Cao
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Shan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051672:Shal Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D051672:Shal Potassium Channels; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases