Figure 2. Cellular calcium content and alternans threshold.

Schematic diagram of the effect of the SR Ca²⁺ content on a proposed model for cellular alternans. Ca²⁺ cycling though calcium-induced-calcium-release (CICR) includes the L-type Ca²⁺ channel, the SR Ca²⁺ ATPase pump (SERCA2a), phospholamban (PLB), the ryanodine receptor (RyR) channel and the Na⁺/Ca²⁺ exchanger (NCX). The solid line shows the SR Ca²⁺ baseline ([Ca²⁺]_SR-base) and the dashed line shows the threshold SR Ca²⁺ ([Ca²⁺]_SR-th) content at which Ca²⁺ release occurs. In the normal heart, CICR is manifested by an operational baseline of [Ca²⁺]_SR that is lower than the threshold to trigger spontaneous Ca²⁺ release. However, high stimulation frequency or β-adrenergic stimulation results in SR Ca²⁺ overload that raises the SR Ca²⁺ baseline level above the threshold such that spontaneous sub-threshold Ca²⁺ release may occur.