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

Na + -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 + ( ) was set to 140 mM. For inwardly directed currents with 105 mM internal K + ( ), the unitary current-voltage relationship was fitted by the constant field equation with a potassium permeability coefficient, P K , of 3.72 × 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 (35 mM ) but it decreased to 181 ± 5.6 pS ( n = 5) in 70 mM (70 mM ). K Na channels were activated by internal Na + in a concentration-dependent fashion. With 4 mM , maximal activation was recorded with 100 mM (open probability, P o , about 0.78); half-maximal activation required about 35 mM . When was increased to 70 mM, half-maximal activation shifted to about 70 mM . With set to 105 mM, channel activity was markedly inhibited when was increased from 35 to 105 mM. Channel openings were abolished with 210 mM . The inhibitory effect of internal K + was also observed at more physiological conditions of osmolarity, ionic strength and chloride concentration. With 35 mM and 4 mM , P o was 0.48 ± 0.10 ( n = 6); when 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 concentration at different levels of is well described by a modified Michaelis-Menten equation for competitive inhibition; the Hill coefficients were 4 for the P o - relationship and 1.2 for the P o - 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 is accompanied by a decrease of .