Seminar Abstract

“Excitation-contraction coupling gain and cooperativity of the Ryanodine receptor: a modeling approach”

Intracellular calcium dynamics is a prime example of a stochastic excitable system. One therefore expects generically to see the spontaneous generation of localized calcium events ("sparks") and/or extended calcium waves, depending on the amplification kinetics and the spatial coupling between release units. Specific calcium-signaling systems, for example cardiac excitation-contraction (EC) coupling, need to be engineered so maximize functionality given this dynamical context.

This talk will review some of the basic phenomenology of stochastic excitable dynamics and then turn to one proposed mechanism by which the EC system maintains gain even while preventing excess leak through spontaneous sparks. Specifically, we show by means of a simplified model that a proper balance between independent and coupled gating of the four Ryanodine subunits can accomplish this task. Experimentally, this balance appears to be regulated by the binding of FKBP; hence our model sheds light on possible diseased states with altered FKBP binding activity.