High Frequency–Induced Upregulation of Human Cardiac Calcium Currents

Abstract

Upregulation of Ca2+ entry through voltage-gated Ca2+ channels by high rates of beating may be involved in the frequency-dependent regulation of contractility (Bowditch "staircase") of the human heart. This process, which is highly sensitive to beta-adrenergic stimulation, may be crucial in adaptation to exercise and stress.

Mechanical alternans and restitution in failing SHHF rat left ventricles

“…The propensity for mechanical alternans, the negative force-frequency relationship, and the prolonged action potentials seen in the failing SHHF rat heart are also observed in failing human hearts (3,9,12,25,26,29,31). Moreover, cardiomyocytes isolated from nonfailing human hearts typically display increases in L-type Ca 2ϩ currents as pacing frequency is increased, whereas cells from failing hearts do not (12,26), suggesting that Ca 2ϩ current facilitation might also be deficient in human heart failure.…”

Diminished post-rest potentiation of contractile force in human dilated cardiomyopathy. Functional evidence for alterations in intracellular Ca2+ handling.

“…Increasing stimulation frequencies result in an increase in time-averaged Ca 2ϩ entry across the sarcolemmal membrane via L-type Ca channels (62,63). An increased amount of Ca 2ϩ within the cell increases Ca 2ϩ loading of the SR.…”

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure

“…The mechanism of these sustained focal discharges likely is L-type calcium current(I Ca-L ) facilitation during repetitive high-rate activations. 16 The increased I Ca-L helps to increase Ca i and the NCX current, sustaining the triggered activity. The mechanisms of frequency-dependent facilitation of I Ca-L were thought to reflect reduced Cadependent inactivation related to reduced Ca load and sarcoplasmic reticulum Ca release.…”