Article date: December 1991
By: Patience E. Tiku, Peter T. Nowell, in Volume 104, Issue 4, pages 895-900
The effects of bretylium were investigated on purified Na,K‐ATPase from guinea‐pig heart and on the Na/K pump in trout erythrocytes, with a view to further identifying the mechanism(s) associated with its antiarrhythmic effects.
Na,K‐ATPase activity of the thiocyanate‐dispersed enzyme was determined by the measurement of inorganic phosphate produced by ATP hydrolysis.
When the concentrations of each of the Na,K‐ATPase activating components were varied in turn, bretylium (1–5 mmol l−1) exhibited competitive‐type effects against K+ with a Ki of 1.4 mmol l−1 and noncompetitive‐type effects against Na+, Mg2+ and ATP.
In K+ influx studies in trout erythrocytes with 86Rb+ used as the marker, the inhibition of total influx observed with bretylium (5 and 10 mmol l−1) was attributable to the bretylium cation selectively inhibiting the Na/K pump‐mediated influx with the associated tosylate anion inhibiting Na/K cotransport.
The observed inhibition kinetics indicated that the bretylium cation (2–15 mmol l−1) competitively inhibited K+ stimulation of the Na/K pump at 6 and 1.25 mmol l−1 external K+ with a mean K1 of 2.3 mmol l−1.
The effects demonstrated on the functioning Na/K pump in erythrocytes confirmed the Na,K‐ATPase findings, with bretylium selectively inhibiting K+ stimulation of the pump mechanism in both cases.
It is suggested that Na,K‐ATPase inhibition may contribute to the antiarrhythmic and positive inotropic effects of bretylium with the cardiac accumulation of bretylium also possibly being a further important factor.
The effects of bretylium were investigated on purified Na,K‐ATPase from guinea‐pig heart and on the Na/K pump in trout erythrocytes, with a view to further identifying the mechanism(s) associated with its antiarrhythmic effects.
Na,K‐ATPase activity of the thiocyanate‐dispersed enzyme was determined by the measurement of inorganic phosphate produced by ATP hydrolysis.
When the concentrations of each of the Na,K‐ATPase activating components were varied in turn, bretylium (1–5 mmol l−1) exhibited competitive‐type effects against K+ with a Ki of 1.4 mmol l−1 and noncompetitive‐type effects against Na+, Mg2+ and ATP.
In K+ influx studies in trout erythrocytes with 86Rb+ used as the marker, the inhibition of total influx observed with bretylium (5 and 10 mmol l−1) was attributable to the bretylium cation selectively inhibiting the Na/K pump‐mediated influx with the associated tosylate anion inhibiting Na/K cotransport.
The observed inhibition kinetics indicated that the bretylium cation (2–15 mmol l−1) competitively inhibited K+ stimulation of the Na/K pump at 6 and 1.25 mmol l−1 external K+ with a mean K1 of 2.3 mmol l−1.
The effects demonstrated on the functioning Na/K pump in erythrocytes confirmed the Na,K‐ATPase findings, with bretylium selectively inhibiting K+ stimulation of the pump mechanism in both cases.
It is suggested that Na,K‐ATPase inhibition may contribute to the antiarrhythmic and positive inotropic effects of bretylium with the cardiac accumulation of bretylium also possibly being a further important factor.
DOI: 10.1111/j.1476-5381.1991.tb12523.x
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