Evidence for a non-capacitative Ca2+ entry during [Ca2+] oscillations.
Current models for the agonist-induced activation of Ca2+ entry from the extracellular medium in non-excitable cells generally emphasize a capacitative mechanism whereby Ca2+ entry is activated simply as a result of the emptying of intracellular Ca2+ stores, without any direct involvement of inositol phosphates. To date, the activation and control of Ca2+ entry have generally been studied under conditions where the agonist-sensitive stores undergo a profound and sustained depletion. However, responses under more normal physiological conditions typically involve the cyclical release and refilling of the stores associated with oscillations in [Ca2+], and the nature and control of entry under these conditions has received relatively little attention. In this study, using isolated cells from the exocrine avian nasal gland as a model system, we show that: (a) the agonist-enhanced rate of Mn2+ quench is independent of the cyclical emptying and refilling of the agonist-sensitive Ca2+ pool during oscillations; (b) the Ca2+ entry pathway is maintained in an activated state for extended periods following inhibition of oscillations under conditions in which agonist-sensitive stores can be shown to be full; (c) no Ca2+ entry could be detected in oscillating cells in experiments that followed a definitive protocol for the demonstration of capacitative entry; and (d) on initial exposure to low agonist concentrations, activation of Ca2+ entry preceded any detectable release of Ca2+ from the stores. We conclude that the essential characteristics of the control of Ca2+ entry during oscillations are incompatible with current capacitative models.
Shuttleworth
T J
TJ
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Thompson
J L
JL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004372:Ducks; D005456:Fluorescent Dyes; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009991:Oscillometry; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D007093:Imidazoles; D007211:Indoles; D008345:Manganese; D002217:Carbachol; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; C048960:indo-1; D002118:Calcium