Summing Across Different Active Zones can Explain the Quasi-Linear Ca2+-Dependencies of Exocytosis by Receptor Cells

Heinrich Neubauer,Peter Heil

doi:10.3389/fnsyn.2010.00148

Abstract

Several recent studies of mature auditory and vestibular hair cells (HCs), and of visual and olfactory receptor cells, have observed nearly linear dependencies of the rate of neurotransmitter release events, or related measures, on the magnitude of Ca2+-entry into the cell. These relationships contrast with the highly supralinear, third to fourth power, Ca2+-dependencies observed in most preparations, from neuromuscular junctions to central synapses, and also in HCs from immature and various mutant animals. They also contrast with the intrinsic, biochemical, Ca2+-cooperativity of the ubiquitous Ca2+-sensors involved in fast exocytosis (synaptotagmins I and II). Here, we propose that the quasi-linear dependencies result from measuring the sum of several supralinear, but saturating, dependencies with different sensitivities at individual active zones of the same cell. We show that published experimental data can be accurately accounted for by this summation model, without the need to assume altered Ca2+-cooperativity or nanodomain control of release. We provide support for the proposal that the best power is 3, and we discuss the large body of evidence for our summation model. Overall, our idea provides a parsimonious and attractive reconciliation of the seemingly discrepant experimental findings in different preparations.

Highlights

Fast release of neurotransmitter by neurons and by receptor cells via fusion of transmitter-containing vesicles with the cell membrane is a process which depends on calcium (Ca2+)-ions (Katz, 1969)
Our assumption of differentially sensitive active zone (AZ) contributing to the summed response, each operating with the established Ca2+-cooperativity of the ubiquitous Ca2+-sensors involved in exocytosis, provides a parsimonious and attractive explanation for experimental findings in different preparations
The summation model Our model aims to account for both the supralinear and the quasi-linear Ca2+-dependencies of exocytosis reported in different preparations, with a minimum number of plausible differences underlying the different dependencies

Summary

Introduction

Fast release of neurotransmitter by neurons and by receptor cells via fusion of transmitter-containing vesicles with the cell membrane is a process which depends on calcium (Ca2+)-ions (Katz, 1969). The probability or rate of fusion of available ready-release vesicles or of transmitter release events ( referred to as exocytosis) is a function of the concentration of Ca2+-ions “seen” by the Ca2+-sensor (e.g., Beutner et al, 2001; Duncan et al, 2010). This concentration depends on a number of factors, including the amount of Ca2+ which enters the cell and the spatial and temporal profile of Ca2+-spread within the cell. The conflicting reports about the relationship between Ca2+-entry and exocytosis in different experimental preparations and their potential cause are the focus of this theoretical paper

Results

Discussion

Conclusion