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Potassium changes the relationship between receptor occupancy and the inotropic effect of cardiac glycosides in guinea‐pig myocardium
Author(s) -
Bachmaier A.,
Ebner F.,
Reiter M.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb11073.x
Subject(s) - ouabain , inotrope , chemistry , endocrinology , medicine , potassium , stimulation , antagonism , sodium , receptor , biology , biochemistry , organic chemistry
1 K + (2.4–15.6 mmol l −1 ) antagonized the positive inotropic effect of dihydro‐ouabain. The concentration‐effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol l −1 Ca 2+ , an increase in K + from 2.4 to 12 mmol l −1 required tenfold higher concentrations of dihydro‐ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol l −1 Ca 2+ . The same change in K + concentration, at 1.2 mmol l −1 Ca 2+ , diminished the inotropic effect of ouabain on rested‐state contractions by a factor of six. 2 The positive inotropic effect of Ca 2+ was also antagonized by K + (1.2–12 mmol l −1 ). Reduction of Na + from 140 to 70 mmol l −1 abolished the antagonistic action of K + (1.2–8.0 mmol l −1 ) Moreover the inotropic effect of Ca 2+ was enhanced. 3 Reduction of Na + , from 140 to 70 mmol l −1 , antagonized the positive inotropic effect of dihydro‐ouabain more at low (2.4 mmol l −1 ) than at high (8.0 mmol l −1 ) K + . Accordingly, the extent of the dihydro‐ouabain‐K + antagonism was reduced. 4 When the K + concentration was increased from 2.4 to 12 mmol l −1 , [ 3 H]‐ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro‐ouabain. 5 Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K + . Diminution of of the action potential was observed only at K + concentrations greater than 5.9 mmol 1 −1 , whereas the resting membrane potential was continuously depolarized over the entire range of K + concentrations. 6 The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K + . Impairment of passive Na + influx during diastole, due to the K + ‐dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside‐K + antagonism.