The influence of membrane lipid metabolites on lymphocyte potassium channel activity.

In the present study, the whole-cell patch-clamp technique was applied to elucidate modulatory effects of high-density lipoproteins (HDL), sphingosine (SPH), sphingosine-1-phosphate (SPP), lysophosphatidic acid (LPA) and sphingosyl- phosphorylcholine (SPC) on the activity of Kv1.3 channels in human T lymphocytes (TL). Obtained data provide evidence that application of SPC at micromolar concentrations shifts the channel activation midpoint by about 20 mV towards positive membrane potentials. This effect occurs in a concentration-dependent manner and is saturated at SPC concentrations higher than 10 micro M. The shift of channel activation midpoint is accompanied by a pronounced slowing of the activation kinetics. The modulatory effect of SPC is clearly voltage-dependent, being most potent at -20 mV and least potent at +60 mV. The steady-state inactivation curve is also shifted by about 20 mV towards positive membrane potentials. The kinetics of channel inactivation and deactivation (closure) remain unaffected upon SPC treatment. In contrast, application of HDL (250 micro g/ml), SPH (50 and 100 micro M), SPP (10 micro M) and LPA (10 and 36 micro M) does not exert any modulatory effect on the channel activity. The effect of SPC on Kv1.3 channel gating resembles the effect exerted by extracellular zinc at the concentration of 10 micro M. It is concluded that the effect of SPC is specific and may be due to the presence of a choline residue in SPC molecules. The possible mechanism and the physiological significance of this modulatory effect on Kv1.3 channels are discussed.