Potassium inhibition of sodium-activated potassium (K(Na)) channels in guinea-pig ventricular myocytes

X W Niu, R W Meech

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalJournal of Physiology
Volume526 Pt 1
Publication statusPublished - 1 Jul 2000

Keywords

  • Adenosine Triphosphate
  • Animals
  • Cells, Cultured
  • Guinea Pigs
  • Heart Ventricles
  • Intracellular Fluid
  • Lithium
  • Meglumine
  • Membrane Potentials
  • Myocardium
  • Osmolar Concentration
  • Patch-Clamp Techniques
  • Perfusion
  • Potassium
  • Potassium Channels
  • Sodium

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