Ca2+ current versus Ca2+ channel cooperativity of exocytosis.
Recently there has been significant interest and progress in the study of spatiotemporal dynamics of Ca(2+) that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca(2+) influx. While varying extracellular or intracellular Ca(2+) concentration assesses the intrinsic biochemical Ca(2+) cooperativity of neurotransmitter release, varying the number of open Ca(2+) channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca(2+) channels in triggering exocytosis. Despite the wide use of these Ca(2+) sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca(2+) sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca(2+) current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca(2+) current magnitude, and the underlying Ca(2+) channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use three-dimensional computational modeling of buffered Ca(2+) diffusion to analyze these distinct Ca(2+) cooperativity measures, and demonstrate the role of endogenous Ca(2+) buffers on such measures. We show that buffers can either increase or decrease the Ca(2+) current cooperativity of exocytosis, depending on their concentration and the single-channel Ca(2+) current.
Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102-1982, USA. matveev@njit.edu
Victor
V
Matveev
Richard
R
Bertram
Arthur
A
Sherman
D000200:Action Potentials / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D008959:Models, Neurological
D015220:Calcium Channels; D002118:Calcium