Submicroscopic Ca²⁺ diffusion mediates inhibitory coupling between individual Ca²⁺ channels

Dihydropyridine-sensitive Ca²⁺ channels in heart demonstrate an important negative feedback property: they close, or inactivate, in response to prior Ca²⁺ entry. We now find that Ca²⁺ influx through one channel can selectively contribute to the inactivation of another adjacent channel, without a generalized elevation of bulk intracellular Ca²⁺ concentration. Intracellular application of the Ca²⁺ chelator BAPTA greatly diminishes such negative interactions within Ca²⁺ channel pairs. These findings demonstrate that Ca²⁺ currents are controlled not only by intrinsic channel properties, but also by local diffusive interactions among neighboring channels. Such inhibitory coupling among channels provides a concrete example of localized Ca²⁺ signaling, long proposed to exist on the basis of theoretical calculations.