A large, multiple-conductance chloride channel in normal human T lymphocytes.
Chloride (Cl) channels have been proposed to play roles in lymphocyte functions including volume regulation and cellular cytotoxicity; however, direct studies of such channels in normal human lymphocytes are lacking. In the present study we describe a large conductance Cl channel observed in about 50% of excised, inside-out patches from normal human peripheral T lymphocytes. The channel has multiple conductance states with linear single-channel current-versus-voltage relationships in symmetrical Cl solutions. The most prevalent state is the largest, which has a conductance of about 365 pS. The channel closes in a voltage-dependent manner at both negative and positive potentials, but does not show voltage-dependent inactivation. The probability of opening is maximal between -15 mV and +15 mV and the voltage dependence is well described by two Boltzmann equations with half-maximal probabilities at -22.8 mV and +18.0 mV. The slopes of the voltage dependence suggest two gates in series with 5.7 and 9.6 equivalent charges. The channel was about 30 times more selective for Cl- than for Na+ or K+ under balanced osmolarity but less selective (approx. 11:1) under a large osmotic gradient. The single-channel conductance increased with Cl concentration with an apparent saturation at about 581 pS and a Michaelis-Menten constant of about 120 mM. The selectivity sequence among anions, determined from changes in reversal potential was: I- greater than NO3- greater than Br-, Cl- greater than F-, isethionate, HCO3- greater than SO4(2-) greater than gluconate, propionate greater than aspartate much greater than Na+, K+ and was apparently the same for subconductance states.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of Toronto, Ontario, Canada.
L C
LC
Schlichter
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R
Grygorczyk
P A
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Pahapill
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Grygorczyk
D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
D002712:Chlorides; D007473:Ion Channels