Spatial calcium buffering in saccular hair cells

Abstract

The potential importance of intracellular calcium-binding proteins in rapid and highly localized Ca2+ signalling is poorly understood. During fast synaptic transmission, which occurs at specialized active zones where Ca2+ diffuses only a few tens of nanometers from channels to neurotransmitter release sites, a cytoplasmic Ca2+ buffer would have to be extremely fast or present in millimolar concentrations to intercept a significant fraction of the calcium ions en route to their targets. Therefore, Ca2+ buffers have been presumed to be unimportant in fast exocytosis and another fast calcium-mediated process, electrical resonance in hair cells. Here I present evidence to the contrary by showing that hair cells in the frog sacculus contain millimolar concentrations of a mobile cytoplasmic calcium buffer that captures Ca2+ within a few microseconds after it enters through presynaptic Ca2+ channels and carries it away from the point of entry. This spatial buffering reduces the presynaptic free Ca2+ by up to 60 per cent and probably restricts the region in which the internal calcium ion concentration exceeds 1 microM to within < 250 nm of each synaptic site. The buffer can thus influence both electrical resonance and synaptic transmission. Calbindin-D28K or a related protein may serve as the mobile calcium buffer, an action similar to its function in transporting Ca2+ across intestinal epithelial cells.

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

“…Because calbindin is a rapid endogenous calcium-buffering protein (Roberts, 1993;Airaksinen et al, 1997;Maeda et al, 1999), at least four types of Ca 2ϩ signals can be affected by calbin- din deficiency. First, as shown above, the AMPAR-mediated calcium transients produced by parallel fiber stimulation in spines and dendrites are distorted.…”

Short-Term Presynaptic Plasticity

“…If present at sufficiently high concentrations, they can bind calcium after it enters through voltage-gated calcium channels and before it reaches release sites (Adler et al 1991;Roberts 1993;Neher 1998). In this way calciumbinding proteins can reduce Ca local at the release site.…”

“…The magnitude of synaptic strength is steeply dependent upon calcium levels, because calcium binds to multiple low-affinity sites on synaptotagmin to trigger vesicle fusion (Jahn et al 2003;Schneggenburger and Neher 2005;Sudhof and Rothman 2009). Ca local is shortlived, is highly sensitive to the distance between open calcium channels and the release site, and can be affected by calcium-binding proteins in the presynaptic bouton (Roberts 1993;Neher 1998;Matveev et al 2004). Calcium-binding proteins with rapid kinetics are particularly effective at intercepting calcium before it can reach release sites, thereby reducing the probability of release (Roberts 1993).…”

“…Ca local is shortlived, is highly sensitive to the distance between open calcium channels and the release site, and can be affected by calcium-binding proteins in the presynaptic bouton (Roberts 1993;Neher 1998;Matveev et al 2004). Calcium-binding proteins with rapid kinetics are particularly effective at intercepting calcium before it can reach release sites, thereby reducing the probability of release (Roberts 1993). After calcium channels close, spatial gradients collapse as calcium diffuses and binds to calcium-binding proteins within the presynaptic bouton (Fogelson and Zucker 1985;Simon and Llinas 1985).…”

[Ca2+]iElevations Detected by BK Channels during Ca2+Influx and Muscarine-Mediated Release of Ca2+from Intracellular Stores in Rat Chromaffin Cells

“…This approach has been used in past studies to demonstrate coupling between Ca 2ϩ and BK channels in the frog hair cell (Roberts, 1993) and between Ca 2ϩ channels and secretory vesicles in the terminals of the squid giant axon (Adler et al, 1991).…”