Potassium inhibition of sodium-activated potassium (K(Na)) channels in guinea-pig ventricular myocytes.
N(a+)-activated potassium channels (K(Na) channels) were studied in inside-out patches from guinea-pig ventricular myocytes at potentials between -100 and +80 mV. External K(+) (K(+)(o)) was set to 140 mM. For inwardly directed currents with 105 mM internal K(+) (K(+)(1)), the unitary current-voltage relationship was fitted by the constant field equation with a potassium permeability coefficient, P(K), of 3.72 x 10(-13) cm(3) s(-1). The slope conductance (-100 to -10 mV) was 194 +/- 4.5 pS (mean +/- s.d., n = 4) with 105 mM K(+)(i) (35 mM Na(+)(i)) but it decreased to 181 +/- 5.6 pS (n = 5) in 70 mM K(+)(i) (70 mM Na(+)(i)). K(Na) channels were activated by internal Na(+) in a concentration-dependent fashion. With 4 mM K(+)(i), maximal activation was recorded with 100 mM Na(+)(i) (open probability, P(o), about 0.78); half-maximal activation required about 35 mM Na(+)(i). When K(+)(i) was increased to 70 mM, half-maximal activation shifted to about 70 mM Na(+)(i). With Na(+)(i) set to 105 mM, channel activity was markedly inhibited when K(+)(i) was increased from 35 to 105 mM. Channel openings were abolished with 210 mM K(+)(i). The inhibitory effect of internal K(+) was also observed at more physiological conditions of osmolarity, ionic strength and chloride concentration. With 35 mM Na(+)(i) and 4 mM K(+)(i), P(o) was 0.48 +/- 0.10 (n = 6); when K(+)(i)was increased to 35 mM, P(o) was reduced to 0.04 +/- 0.05 (n = 7, P < 0.001). The relationship between P(o) and Na(+)(i) concentration at different levels of K(+)(i) is well described by a modified Michaelis-Menten equation for competitive inhibition; the Hill coefficients were 4 for the P(o)-Na(+)(i) relationship and 1.2 for the P(o)-K(+)(i) relationship. It is suggested that Na(+) and K(+) compete for a superficial site on the channel's permeation pathway. K(Na) channels would be most likely to be activated in vivo when an increase in Na(+)(i) is accompanied by a decrease of K(+)(i).
Niu
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XW
Department of Physiology, University Walk, Bristol BS8 1TD, UK.
Meech
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RW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010477:Perfusion; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology
D015221:Potassium Channels; D008536:Meglumine; D000255:Adenosine Triphosphate; D008094:Lithium; D012964:Sodium; D011188:Potassium