Home LiteratureArticle Details
PMID: 10096899 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Presynaptic strontium dynamics and synaptic transmission.

Biophysical journal ·Vol. 76 ·No. 4 ·1999-04-00 ·Pages 2029-42

Xu-Friedman MA, Regehr WG

Abstract

Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium.

MeSH Terms
Animals Biophysical Phenomena Biophysics Calcium/metabolism,pharmacology Calcium Signaling Chelating Agents/pharmacology Egtazic Acid/pharmacology Fluorescent Dyes Fura-2 In Vitro Techniques Kinetics Mice Mice, Inbred ICR Models, Neurological Neurotransmitter Agents/metabolism Presynaptic Terminals/drug effects,physiology Purkinje Cells/drug effects,metabolism,physiology Signal Transduction Strontium/pharmacology Synaptic Transmission/drug effects,physiology
Chemicals
Chelating Agents Fluorescent Dyes Neurotransmitter Agents Egtazic Acid Calcium Fura-2 Strontium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Xu-Friedman M A
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Regehr W G
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(99)77360-1
Published
1999-04-00
Pages
2029-42
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1300177
Subset
IM
Grants
NINDS NIH HHS · 5T32 NS07112-19 · United States
NINDS NIH HHS · R01-NS32405-01 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(99)77360-1 PMC Full Text View journal details
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