Voltage-gated Ca 2+ currents in the human pathophysiologic heart: a review

The L-type Ca ²⁺ current (I _Ca-L) plays a key role in the cardiac excitation-contraction (E-C) coupling. Thus, it is a major target for many transmitters and hormones modulating cardiac function and, therefore, for pharmacological drugs to regulate inotropy. Ca ²⁺ (and other) ion currents are commonly studied in animal tissues for practical reasons. Investigations in human cardiomyocytes started extensively only ten years ago with the development of patch-clamp techniques, enzymatic cell dissociation procedures, and surgical techniques. These studies have already provided valuable information concerning the nature, biophysics, pharmacology and regulation of human cardiac ionic currents in normal and diseased tissues. Interesting advances have been made to understand the role of I _Ca-L in the development of chronic atrial fibrillation (AF). Alterations of single channel activity and regulation of macroscopic I _Ca-L have also been found in heart failure (HF), although some of the data are divergent and puzzling. The T-type Ca ²⁺ current (I _Ca-T) has never been recorded in human cardiomyocytes. After a rapid overview of the basic properties of human cardiac Ca ²⁺ currents, we focus on selected aspects of pathophysiology that are still unsolved.