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Am J Physiol. 1995 Nov;269(5 Pt 1):C1079-92.

Ca2+ excitability of the ER membrane: an explanation for IP3-induced Ca2+ oscillations.

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1
Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Recent research dealing with experiments and theoretical models of Ca2+ excitability of the endoplasmic reticulum (ER) membrane induced by inositol 1,4,5-trisphosphate (IP3) is reviewed. Ca2+ excitability refers to the ability of a small increment of cytoplasmic Ca2+ concentration ([Ca2+]i) to trigger a large [Ca2+]i pulse or oscillations. Such nonlinear regenerative behavior is conferred by the existence of IP3 channels and Ca(2+)-ATPase transporters on the ER membrane, which extends throughout the cytoplasm. Ca2+ excitability resembles the plasma membrane electrical excitability of neurons and other cells: it is driven by the ionic concentration gradient across the ER membrane (higher Ca2+ concentration inside the ER); each [Ca2+]i spike partially consumes the prestored energy that is reestablished through ATP-dependent active transport; and [Ca2+]i, the excitation variable, controls the nonlinear dynamic release rate of ER Ca2+. This review focuses on the kinetic models based on these features and on experiments dealing with the kinetic properties of [Ca2+]i-dependent gating of the IP3 receptor channel. We summarize evidence in favor of two roles for [Ca2+]i in gating the channel's opening: activation at a rapid time scale and inactivation on a slower time scale. Exploiting an analogy to the well-known Hodgkin-Huxley model for neuronal electrical excitability, we show how Ca2+ excitability of the ER membrane can be explained by these gating properties combined with the ER Ca2+ pump activity. The theory's ability to predict is illustrated by comparing calculated with experimental [Ca2+]i responses for pituitary gonadotrophs under various stimulus conditions.

[Indexed for MEDLINE]

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