Faculty Collaboration Database

Multiple modes of calcium-induced calcium release in sympathetic neurons I: attenuation of endoplasmic reticulum Ca2+ accumulation at low [Ca2+](i) during weak depolarization. J Gen Physiol 2001 Jul;118(1):83-100

Date

06/29/2001

Pubmed ID

11429446

Pubmed Central ID

PMC2233742

DOI

10.1085/jgp.118.1.83

Scopus ID

2-s2.0-0034930823 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

Many cells express ryanodine receptors (RyRs) whose activation is thought to amplify depolarization-evoked elevations in cytoplasmic Ca2+ concentration [Ca2+](i) through a process of Ca2+ -induced Ca2+ release (CICR). In neurons, it is usually assumed that CICR triggers net Ca2+ release from an ER Ca2+ store. However, since net ER Ca 2+ transport depends on the relative rates of Ca2+ uptake and release via distinct pathways, weak activation of a CICR pathway during periods of ER Ca accumulation would have a totally different effect: attenuation of Ca2+ accumulation. Stronger CICR activation at higher [Ca2+](i) could further attenuate Ca2+ accumulation or trigger net Ca2+ release, depending on the quantitative properties of the underlying Ca2+ transporters. This and the companion study (Hongpaisan, J., N.B. Pivovarova, S.L. Colgrove, R.D. Leapman, and D.D. Friel, and S.B. Andrews. 2001. J. Gen. Physiol. 118:101-112) investigate which of these CICR "modes" operate during depolarization-induced Ca2+ entry in sympathetic neurons. The present study focuses on small [Ca2+](i) elevations (less than approximately 350 nM) evoked by weak depolarization. The following two approaches were used: (1) Ca2+ fluxes were estimated from simultaneous measurements of [Ca2+](i) and I(Ca) in fura-2-loaded cells (perforated patch conditions), and (2) total ER Ca concentrations ([Ca](ER)) were measured using X-ray microanalysis. Flux analysis revealed triggered net Ca2+ release during depolarization in the presence but not the absence of caffeine, and [Ca2+](i) responses were accelerated by SERCA inhibitors, implicating ER Ca2+ accumulation, which was confirmed by direct [Ca](ER) measurements. Ryanodine abolished caffeine-induced CICR and enhanced depolarization-induced ER Ca2+ accumulation, indicating that activation of the CICR pathway normally attenuates ER Ca2+ accumulation, which is a novel mechanism for accelerating evoked [Ca2+](i) responses. Theory shows how such a low gain mode of CICR can operate during weak stimulation and switch to net Ca2+ release at high [Ca2+](i), a transition demonstrated in the companion study. These results emphasize the importance of the relative rates of Ca2+ uptake and release in defining ER contributions to depolarization-induced Ca2+ signals.

Author List

Albrecht MA, Colegrove SL, Hongpaisan J, Pivovarova NB, Andrews SB, Friel DD

Author

Meredith A. Albrecht MD, PhD Associate Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Caffeine
Calcium
Calcium Signaling
Cell Membrane
Central Nervous System Stimulants
Cytoplasm
Dose-Response Relationship, Drug
Electron Probe Microanalysis
Electrophysiology
Endoplasmic Reticulum
Neurons
Rana catesbeiana
Ryanodine
Ryanodine Receptor Calcium Release Channel
Sympathetic Nervous System