Molecular Medicine FKBP12 Is a Critical Regulator of the Heart Rhythm and the Cardiac Voltage-Gated Sodium Current in Mice
نویسندگان
چکیده
voltage-gated sodium current INa in MyHC-FKBP12 ventricular cardiomyocytes, a slower recovery of INa from inactivation, shifts of steady-state activation and inactivation curves of INa to more depolarized potentials, and augmentation of late INa, suggesting that the arrhythmogenic phenotype of MyHC-FKBP12 mice is attributable to abnormal INa. Ventricular cardiomyocytes isolated from FKBP12 / MyHC-Cre hearts showed faster action potential upstrokes and a more than 2-fold increase in peak INa density. Dialysis of exogenous recombinant FKBP12 protein into FKBP12-deficient cardiomyocytes promptly recapitulated
منابع مشابه
FKBP12 is a critical regulator of the heart rhythm and the cardiac voltage-gated sodium current in mice.
RATIONALE FK506 binding protein (FKBP)12 is a known cis-trans peptidyl prolyl isomerase and highly expressed in the heart. Its role in regulating postnatal cardiac function remains largely unknown. METHODS AND RESULTS We generated FKBP12 overexpressing transgenic (αMyHC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditional knockout (FKBP12(f/f)/αMyHC-Cre) mice and analyzed their cardia...
متن کاملInherited sodium channelopathies: novel therapeutic and proarrhythmic molecular mechanisms.
Voltage-gated sodium (Na) channels, transmembrane proteins that produce the ionic current responsible for the rapid upstroke of the cardiac action potential, are key elements required for rapid conduction through the myocardium and maintenance of the cardiac rhythm. The exquisite sensitivity of the cardiac rhythm to Na channel function is manifest in the proarrhythmic complications of "antiarrh...
متن کاملVoltage-Gated Sodium Channels Modulation by Bothutous Schach Scorpion Venom
Buthotus schach is one of the dangers scorpion in Iran that belong to the Buthidae family. Toxins are existing in venom scorpion, modulate the ion channels by blocking or opening the pore of the channel or by altering the voltage gating and useful as pharmacological tools. In the present study, we investigated the effect of venom and its obtained fractions by gel filtrations on electrophysiolog...
متن کاملTemperature-dependent model of human cardiac sodium channel
Cardiac sodium channels are integral membrane proteins whose structure is not known at atomic level yet and their molecular kinetics is still being studied through mathematical modeling. This study has focused on adapting an existing model of cardiac Na channel to analyze molecular kinetics of channels at 9-37°C. Irvine et al developed a Markov model for Na channel using Neuronal Network Model ...
متن کاملTemperature-dependent model of human cardiac sodium channel
Cardiac sodium channels are integral membrane proteins whose structure is not known at atomic level yet and their molecular kinetics is still being studied through mathematical modeling. This study has focused on adapting an existing model of cardiac Na channel to analyze molecular kinetics of channels at 9-37°C. Irvine et al developed a Markov model for Na channel using Neuronal Network Model ...
متن کامل