• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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.

Pubmed ID: 19793978


  • Matveev V
  • Bertram R
  • Sherman A


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

September 30, 2009

Associated Grants

  • Agency: Intramural NIH HHS, Id: Z01 DK013028-02

Mesh Terms

  • Action Potentials
  • Calcium
  • Calcium Channels
  • Calcium Signaling
  • Exocytosis
  • Models, Neurological