“Control of Calcium in the Heart – Free and Beyond”
Hosted by the Cardiac Bioelectricity and Arrhythmia Center (CBAC)
Abstract: David Eisner will begin the presentation by reviewing how calcium is used to regulate cell function. Since calcium cannot be destroyed, regulation of its concentration requires pumping across membranes. Importantly, on each heartbeat, the amount of calcium that enters the cell must exactly equal that which leaves. The lecture will discuss the consequences that this has for cardiac function.
99% of the calcium in the cytoplasm is bound to buffers. It is often not appreciated that the magnitude of the change of free calcium concentration depends as much on the properties of the calcium buffers as on the underlying fluxes.
Most of the Ca that activates contraction is derived from the sarcoplasmic reticulum (SR) and is released by the process of Ca induced Ca release (CICR) through the Ryanodine Receptor (RyR). On this mechanism, Ca enters the cell via the L-type Ca current and binds to the RyR making it open thereby resulting in the release of a much larger amount of Ca from the SR. The amount of Ca released depends on many factors including the properties of the RyR and the Ca content of the SR. Eisner will discuss both the control of SR Ca content and the relationship between SR Ca content and the amplitude of the Ca transient.
It is also important that during diastole, Ca is lowered to levels sufficiently low that the heart can relax and refill with blood. The mechanisms that control diastolic Ca are, however, much less well understood. Eisner will present data suggesting that diastolic Ca is indirectly controlled by the level of systolic Ca. Specifically, reducing the systolic Ca release will decrease Ca efflux from the cell thereby tending to increase diastolic Ca. This may explain why making the RyR leaky or inhibiting SR Ca-ATPase activity elevate diastolic while decreasing systolic Ca.
For inquiries contact Huyen Nguyen.