[Effect of intracellular trypsin on characteristics of voltage-dependent inactivation of chloride currents in prostatic cancer cells].
By means of the patch-clamp technique we have studied the effects of intracellular applied trypsin, a known modulator of membrane channel function, on the properties of the Cl- current induced by hypotonicity-obliged cell swelling (ICl, swell) in human prostate cancer epithelial cells, LNCaP. Intracellular infusion of 1 mg/ml of trypsin into LNCaP cells via the patch pipette shortened the delay for the onset and the time of development of ICl, swell in response to hypotonicity as well as accelerated the rate of current diminution following the return to isotonic conditions. The maximal density of ICl, swell in the presence of intracellular trypsin was 2-fold higher while the current voltage-dependent inactivation at high depolarizing potentials was virtually eliminated. Intracellular co-application of the trypsin inhibitor together with trypsin abolished all effects of trypsin. We conclude that VRACs share a great degree of functional and structural homology to voltage-gated Na+, K+ and Cl- channels by having intracellular inactivation domain subjected to proteolytic cleavage that function in conformity with "ball-and-chain" inactivation model.
Vitko
Iu M
IuM
A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kiev.
Lazarenko
R M
RM
Pohorila
N Kh
NKh
D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009994:Osmolar Concentration; D011471:Prostatic Neoplasms / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D018118:Chloride Channels; D014357:Trypsin