Electrophysiological aspects of changes in heart rate.

Cardiac action potentials undergo characteristic changes in response to increasing pacing frequency, i.e., the resting potential becomes less negative (depolarization), the amplitude decreases, and the action potential duration (APD) shortens. The electrophysiological properties of the major cardiac inward and outward currents are discussed with respect to their possible contribution to rate-dependent changes in AP shape. Short diastolic intervals may not allow sufficient time for channel recovery. Incomplete recovery from inactivation will reduce both inward (INa, ICa) and outward (Ito) currents and hence lead to APD shortening or prolongation, respectively. Incomplete deactivation during diastole will increase current and, in the case of the delayed rectifier IKs, produces rate-dependent APD shortening. Heterogeneity in current density of myocytes from various regions within the ventricular wall complicates the direct translation of rate-dependent changes in APD into changes of the QT interval of the ECG. With increasing rates of stimulation, K+ accumulates within the tubular system. Membrane depolarization may be attributed to this frequency-dependent increase in [K+]o, whereas APD shortening is not mimicked by high [K+]o. Nevertheless, the various cardiac K+ channels differ in their sensitivity to extracellular [K+]o. Some of the frequency-dependent effects of drugs with class III action may be related to an influence of [K+]o on drug potency to block K+ channels.