CALCIUM CURRENT IN SINGLE HUMAN CARDIAC MYOCYTES

Introduction: Significant species-, tissue-, and age-dependent differe nces have been described for the L-type calcium current (I(Ca)). There fore, extrapolation of data obtained from the many animal models to hu man cardiac physiology is difficult. In this study, we have characteri zed the voltage-dependent properties of I(Ca) from and adult, atrial a nd ventricular human heart tissue. Methods and Results: I(Ca) was meas ured in single human heart muscle cells using the ''whole cell,'' volt age clamp method. Single myocytes were isolated from myocardial specim ens 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 wa s between -80 and -85 mV. The action potential shape and duration and current-voltage relationship for I(Ca) were similar to that reported b y others for human heart cells. The steady-state activation variable, d(infinity), was found to be similar in both pediatric atrial and vent ricular cells but shifted approximately 5 mV negative in the adult atr ial and ventricular cells. I(Ca) of all cells displayed biexponential inactivation and steady-state inactivation was incomplete at positive potentials (steady-state inactivation curves turned up at positive pot entials) consistent with inactivation arising from voltage-dependent a nd calcium-dependent processes as reported in heart cells from many sp ecies. The potential of maximal inactivation was more negative for adu lt cells (around -10 mV) than pediatric cells (around 0 mV). Estimates of the calcium ''window'' current, using a modified Hodgkin-Huxley mo del, could explain measured differences in action potential shape and duration. Conclusion: Human cardiac I(Ca) can be investigated using wh ole cell, voltage clamp methods and a modified Hodgkin-Huxley model. Q uantitative characterization of many of the properties of I(Ca) in hum an heart tissue suggests that important species differences do exist a nd that further investigations are required to characterize the depend ence of inactivation on [Ca2+]i in human heart cells. Since the array of characteristics of I(Ca) in different species varies, the study of human myocardial cells per se continues to be important when examining human cardiac physiology.