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Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells
Author(s) -
Bird Gary St. J.,
Putney James W.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.077289
Subject(s) - trpc3 , extracellular , calcium , biophysics , chemistry , intracellular , calcium in biology , calcium signaling , methacholine , microbiology and biotechnology , medicine , endocrinology , biology , receptor , trpc , biochemistry , transient receptor potential channel , respiratory disease , organic chemistry , lung
Treatment of human epithelial kidney (HEK293) cells with low concentrations of the muscarinic agonist methacholine results in the activation of complex and repetitive cycling of intracellular calcium ([Ca 2+ ] i ), known as [Ca 2+ ] i oscillations. These oscillations occur with a frequency that depends on the concentration of methacholine, whereas the magnitude of the [Ca 2+ ] i spikes does not. The oscillations do not persist in the absence of extracellular Ca 2+ , leading to the conclusion that entry of Ca 2+ across the plasma membrane plays a significant role in either their initiation or maintenance. However, treatment of cells with high concentrations of GdCl 3 , a condition which limits the flux of calcium ions across the plasma membrane in both directions, allows sustained [Ca 2+ ] i oscillations to occur. This suggests that the mechanisms that both initiate and regenerate [Ca 2+ ] i oscillations are intrinsic to the intracellular milieu and do not require entry of extracellular Ca 2+ . This would additionally suggest that, under normal conditions, the role of calcium entry is to sustain [Ca 2+ ] i oscillations. By utilizing relatively specific pharmacological manoeuvres we provide evidence that the Ca 2+ entry that supports Ca 2+ oscillations occurs through the store‐operated or capacitative calcium entry pathway. However, by artificial introduction of a non‐store‐operated pathway into the cells (TRPC3 channels), we find that other Ca 2+ entry mechanisms can influence oscillation frequency in addition to the store‐operated channels.