Calcium-dependent efflux of K+ ions from stimulated T lymphocytes of young and old mice.
The changes in the rate of efflux of potassium cations from ionomycin-, A23187-, and Concanavalin A (Con A)-stimulated lymphocytes from young and old mice were studied with an ion-selective electrode in a 'half-micro' system. It was found that, for both types of stimuli, the maximal rate of Ca(2+)-dependent efflux of K+ from young T cells was more than twice that attained by old cells. A bimodality of the curve illustrating change of efflux rate was observed, indicating possible existence of two types of Ca(2+)-dependent conductances. The kinetics of change of the efflux rate was similar for young and old cells stimulated with calcium ionophores, but differed in the cells stimulated with Con A. There, a lag period between mitogen addition and onset of measurable K+ efflux was absent in the case of old T cells, suggesting that function of other (Ca-independent?) mechanisms of K+ efflux during the mitogen stimulation may also be changed there. The measured efflux of K+ was only partially dependent on the extracellular Ca2+. Also, it was quantitatively different in a 'physiological' medium containing 140 mM Na+, as compared to a sodium-free medium. Different blockers of potassium, calcium and sodium channels had at least partially inhibitory effect on the measured flux. Presented findings indicate that potassium conductance through Ca(2+)-gated K+ channels is impaired in T cells of old mice. Ca(2+)-dependent efflux of K+ in murine T cells is apparently conducted by a specific class of membrane channels, possibly consisting of two types of channels with different activation kinetics and pharmacological sensitivities (expressed in different subpopulations of T cells?). Impaired potassium conductance in old T cells is discussed as one of possible causes of age-related dysfunction of the immune system.
Witkowski
J M
JM
Department of Histology, Medical Academy of Gdansk, Poland.
D000375:Aging / Q000097:blood*; D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D012530:Saxitoxin / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D008934:Mitogens; D003208:Concanavalin A; D014634:Valinomycin; D012530:Saxitoxin; D000001:Calcimycin; D015759:Ionomycin; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D002118:Calcium