AJP - Cell Physiology, Vol 257, Issue 2 C197-C206, Copyright © 1989 by American Physiological Society

ARTICLES

Ca2+ induces charybdotoxin-sensitive membrane potential changes in rat lymphocytes

S. Grinstein and J. D. Smith
Division of Cell Biology, Hospital for Sick Children, Toronto, Canada.

There is disagreement regarding the existence of Ca2+-activated K+ channels in lymphocytes. Depolarization, hyperpolarization, or little change in membrane potential (Em) has been reported following elevation of free cytosolic Ca2+ concentration ([Ca2+]i). Patch-clamping studies have demonstrated inhibition of voltage-gated K+ channels, but Ca2+-activated K+ channels have not been detected. We used charybdotoxin (CTX), a potent inhibitor of Ca2+-activated K+ channels, to assess their presence in rat thymic lymphocytes. Fluorescent probes were used to measure Em and [Ca2+]i in cell suspensions treated with ionomycin. At basal [Ca2+]i, CTX had no effect on Em, suggesting that Ca2+-activated K+ channels do not contribute importantly to the resting potential. Elevation of [Ca2+]i in the submicromolar range induced a hyperpolarization that was dependent on the outward K+ gradient. The shape and duration of the Em change closely followed the elevation of [Ca2+]i. This hyperpolarization was inhibited by nanomolar concentrations of CTX. When [Ca2+]i approached or exceeded 1 microM, a biphasic Em change was recorded. A transient, CTX-sensitive hyperpolarization was followed by a sustained depolarization. The latter was greatly reduced when external Na+ was omitted. The data suggest that thymic lymphocytes possess Ca2+-sensitive K+ channels, which are activated by moderate increases in [Ca2+]i, resulting in hyperpolarization. At higher [Ca2+]i, the effect of K+ channels on Em is superseded by opening of nonselective cation channels, producing depolarization. Variations in the level of [Ca2+]i attained in earlier studies can explain existing discrepancies.

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