Ilona Bodi1, Hiroyuki Nakayama, Arnold Schwartz. 1. *Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and †Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati Medical Center, Cincinnati, OH.
Abstract
AIMS: To obtain functional evidence that ICa,T is involved in the pathogenesis of cardiac hypertrophy and heart failure. We unexpectedly identified ICa(TTX) rather than ICa,T, therefore, we adjusted our aim to encompass these findings. METHODS AND RESULTS: We investigated (1) Cav3.1 (α1G) transgenic (Tg) mice compared with nontransgenic (tTA-Ntg); (2) Cav3.1-deficient mice (Cav3.1) compared with wild type (Wt) after chemically and surgically induced cardiac remodeling; and (3) spontaneous hypertensive rats and thoracic aortic constriction (TAC) rats. Whole-cell patch-clamp technique was used to measure ICa in ventricular myocytes. Cav3.1-Tg expressed ICa,T (-18.35 ± 1.02 pA/pF at -40 mV) without signs of compromised cardiac function. While we failed to detect ICa,T after hypertrophic stimuli, instead we demonstrated that both Wt and Cav3.1 mouse exhibit ICa(TTX). Using TAC rats, only 2 of 24 VMs showed ICa,T under our experimental conditions. Without TTX, ICa(TTX) occurred in VMs from Wt, spontaneous hypertensive rats, and TAC rats also. CONCLUSIONS: These findings demonstrate for the first time that mouse VMs express ICa(TTX). We suggest that future studies should take into consideration the measuring conditions when interpreting ICa,T reappearance in ventricular myocytes in response to hypertrophic stress. Contamination with ICa(TTX) could possibly confuse the relevance of the data.
AIMS: To obtain functional evidence that ICa,T is involved in the pathogenesis of cardiac hypertrophy and heart failure. We unexpectedly identified ICa(TTX) rather than ICa,T, therefore, we adjusted our aim to encompass these findings. METHODS AND RESULTS: We investigated (1) Cav3.1 (α1G) transgenic (Tg) mice compared with nontransgenic (tTA-Ntg); (2) Cav3.1-deficient mice (Cav3.1) compared with wild type (Wt) after chemically and surgically induced cardiac remodeling; and (3) spontaneous hypertensiverats and thoracic aortic constriction (TAC) rats. Whole-cell patch-clamp technique was used to measure ICa in ventricular myocytes. Cav3.1-Tg expressed ICa,T (-18.35 ± 1.02 pA/pF at -40 mV) without signs of compromised cardiac function. While we failed to detect ICa,T after hypertrophic stimuli, instead we demonstrated that both Wt and Cav3.1 mouse exhibit ICa(TTX). Using TAC rats, only 2 of 24 VMs showed ICa,T under our experimental conditions. Without TTX, ICa(TTX) occurred in VMs from Wt, spontaneous hypertensiverats, and TAC rats also. CONCLUSIONS: These findings demonstrate for the first time that mouse VMs express ICa(TTX). We suggest that future studies should take into consideration the measuring conditions when interpreting ICa,T reappearance in ventricular myocytes in response to hypertrophic stress. Contamination with ICa(TTX) could possibly confuse the relevance of the data.
Authors: Geraldine A Fuller-Bicer; Gyula Varadi; Sheryl E Koch; Masakazu Ishii; Ilona Bodi; Nijiat Kadeer; James N Muth; Gabor Mikala; Natalia N Petrashevskaya; Michael A Jordan; Sui-Po Zhang; Ning Qin; Christopher M Flores; Idit Isaacsohn; Maria Varadi; Yasuo Mori; W Keith Jones; Arnold Schwartz Journal: Am J Physiol Heart Circ Physiol Date: 2009-05-08 Impact factor: 4.733
Authors: Ravi Vaidyanathan; Ryan P O'Connell; Makarand Deo; Michelle L Milstein; Philip Furspan; Todd J Herron; Sandeep V Pandit; Hassan Musa; Omer Berenfeld; José Jalife; Justus M B Anumonwo Journal: Heart Rhythm Date: 2012-10-04 Impact factor: 6.343
Authors: Hiroyuki Nakayama; Ilona Bodi; Robert N Correll; Xiongwen Chen; John Lorenz; Steven R Houser; Jeffrey Robbins; Arnold Schwartz; Jeffery D Molkentin Journal: J Clin Invest Date: 2009-11-16 Impact factor: 14.808
Authors: Xiongwen Chen; Rachel M Wilson; Hajime Kubo; Remus M Berretta; David M Harris; Xiaoying Zhang; Naser Jaleel; Scott M MacDonnell; Claudia Bearzi; Jochen Tillmanns; Irina Trofimova; Toru Hosoda; Federico Mosna; Leanne Cribbs; Annarosa Leri; Jan Kajstura; Piero Anversa; Steven R Houser Journal: Circ Res Date: 2007-02-01 Impact factor: 17.367