Ca(2+)-dependent and Ca(2+)-independent mechanisms modulate whole-cell cationic currents in human neutrophils.
We used whole-cell, voltage-clamp methodology to study the activation and inhibition of cationic currents in neutrophil. Cationic channels involved were impermeable to N-methyl-D-glucamine and to choline, but permeable to Na+, K+, Cs+, tris(hydroxymethyl)amino-ethane, and tetraethylammonium. N-formyl-L-methionyl-L-leucyl-L-phenylalanine, the Ca(2+)-ionophore A23187, and phorbol myristate acetate activated the cationic current. Activated currents showed voltage dependence and outward rectification. The Ca(2+)-chelator 1,2 bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate markedly inhibited A23187-induced currents, but only partially decreased phorbol ester- or chemoattractant-induced currents. Dibutyryl cAMP diminished only the chemoattractant-induced currents. The adenosine analogs 5'N-ethylcarboxamidoadenosine and N6-cyclohexyladenosine blocked the currents induced by all agents. Thus, we conclude that activation and inhibition of cationic channels in human neutrophils involve both Ca(2+)-dependent and Ca(2+)-independent mechanisms.
Schumann
M A
MA
Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine.
Tanigaki
T
T
Heller
D N
DN
Raffin
T A
TA
D000227:Adenine Nucleotides / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002412:Cations; D004594:Electrophysiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000227:Adenine Nucleotides; D002412:Cations; D007473:Ion Channels; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium