Voltage clamp analysis of human cardiac myocytes showed steady-state activation shifted ~5 mV negative and maximal inactivation was more negative in adult (-10 mV) versus pediatric (0 mV) cells.
Human cardiac L-type calcium currents exhibit age-dependent differences in steady-state activation and inactivation, highlighting the importance of studying human myocardial cells directly rather than relying solely on animal models.
INTRODUCTION: Significant species-, tissue-, and age-dependent differences have been described for the L-type calcium current (ICa). Therefore, extrapolation of data obtained from the many animal models to human cardiac physiology is difficult. In this study, we have characterized the voltage-dependent properties of ICa from pediatric and adult, atrial and ventricular human heart tissue. METHODS AND RESULTS: ICa was measured in single human heart muscle cells using the "whole cell," voltage clamp method. Single myocytes were isolated from myocardial specimens obtained intraoperatively from both pediatric and adult patients (ages 3 months to 75 years) undergoing cardiac surgery. Cells obtained for these experiments appeared to be healthy; the resting potential was between -80 and -85 mV. The action potential shape and duration and current-voltage relationship for ICa were similar to that reported by others for human heart cells. The steady-state activation variable, d infinity, was found to be similar in both pediatric atrial and ventricular cells but shifted approximately 5 mV negative in the adult atrial and ventricular cells. ICa of all cells displayed biexponential inactivation and steady-state inactivation was incomplete at positive potentials (steady-state inactivation curves turned up at positive potentials) consistent with inactivation arising from voltage-dependent and calcium-dependent processes as reported in heart cells from many species. The potential of maximal inactivation was more negative for adult cells (around -10 mV) than pediatric cells (around 0 mV). Estimates of the calcium "window" current, using a modified Hodgkin-Huxley model, could explain measured differences in action potential shape and duration. CONCLUSION: Human cardiac ICa can be investigated using whole cell, voltage clamp methods and a modified Hodgkin-Huxley model. Quantitative characterization of many of the properties of ICa in human heart tissue suggests that important species differences do exist and that further investigations are required to characterize the dependence of inactivation on Ca2+i in human heart cells. Since the array of characteristics of ICa in different species varies, the study of human myocardial cells per se continues to be important when examining human cardiac physiology.
Cohen et al. (Sun,) conducted a other in Patients undergoing cardiac surgery. Whole cell voltage clamp characterization of ICa vs. Pediatric vs adult cells was evaluated on Voltage-dependent properties of L-type calcium current (ICa). Voltage clamp analysis of human cardiac myocytes showed steady-state activation shifted ~5 mV negative and maximal inactivation was more negative in adult (-10 mV) versus pediatric (0 mV) cells.