SMALL CA2-ACTIVATED POTASSIUM CHANNELS IN HUMAN LEUKEMIC T-CELLS AND ACTIVATED HUMAN PERIPHERAL-BLOOD T-LYMPHOCYTES()

In human T lymphocytes patch-clamp experiments have revealed the expre ssion of two major subtypes of SK channels. In excitable cells these c hannel types play significant roles in shaping excitablility as well a s firing patterns especially since their open probability is regulated by the intracellular second messenger Ca2+. In nonexcitable T cells, SK channels could hyperpolarize the membrane during the rise in [Ca2+] (i) elicited via T-cell receptor stimulation. This hyperpolarization i n turn could contribute to enhanced Ca2+ entry by increasing the drivi ng force for Ca2+ to enter the cell [see also Verheugen, this issue] v ia I-CRAC. This scenario plays an increasingly significant role in alr eady activated T cells due to the up-regulated number of SK channels i n activated human peripheral T lymphocytes. We have used whole-cell re cording to determine the electrophysiological properties of current th rough SKAPA channels in Jurkat T cells and through SKCTX channels in a ctivated HPB T lymphocytes. The main similarities between the two chan nel types are their Ca2+ sensitivity and voltage dependence. The SK ch annel activity depends steeply on [Ca2+](i), suggesting that multiple Ca2+ must bind to the channel or an associated molecule in order to op en the pore. The Ca2+ concentration at which half the channels are act ivated is similar to 400-450 nM and the activity of both channel types is voltage-independent. The major difference between the two channel types is their pharmacology regarding peptide toxins like apamin, scyl latoxin, charybdotoxin, as well as other blockers like TEA(+). SKCTX a nd SKAPA channels show minor differences in Ba2+ sensitivity, inductio n time course, selectivity, and single-channel conductance. All these properties together should allow a better distinction between these tw o different types of SK channels in lymphocytes with the ultimate goal to identify the genes encoding these channels.