β-adrenergic stimulation increases cav3.1 activity in cardiac myocytes through protein kinase aβ-adrenergic刺激心肌细胞动作电位增加cav3.1活动通过蛋白激酶.pdf

b-Adrenergic Stimulation Increases Cav3.1 Activity in Cardiac Myocytes through Protein Kinase A 1. 1. 1 1 1 1 1,2 Yingxin Li , Fang Wang , Xiaoying Zhang , Zhao Qi , Mingxin Tang , Christopher Szeto , Ying Li , 1 1 Hongyu Zhang , Xiongwen Chen * 1 Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma Burns and Combined Injury, Third Military Medical University, Chongqing, China Abstract The T-type Ca2+ channel (TTCC) plays important roles in cellular excitability and Ca2+ regulation. In the heart, TTCC is found in the sinoatrial nodal (SAN) and conduction cells. Cav3.1 encodes one of the three types of TTCCs. To date, there is no report regarding the regulation of Cav3.1 by b-adrenergic agonists, which is the topic of this study. Ventricular myocytes (VMs) from Cav3.1 double transgenic (TG) mice and SAN cells from wild type, Cav3.1 knockout, or Cav3.2 knockout mice were used to study b-adrenergic regulation of overexpressed or native Cav3.1-mediated T-type Ca2+ current (ICa-T(3.1)). ICa- T(3.1) was not found in control VMs but was robust in all examined TG-VMs. A b-adrenergic agonist (isoproterenol, ISO) and a cyclic AMP analog (dibutyryl-cAMP) significantly increased ICa-T(3.1) as well as ICa-L in TG-VMs at both physiological and room temperatures. The ISO effect on ICa-L and ICa-T in TG myocytes was blocked by H89, a PKA inhibitor. ICa-T was detected in control wildtype SAN cells but not in Cav3.1 knockout SAN cells, indicating the identity o