Alteration of Na +, K +-dependent ATPase activity and inotropism by polyethylene glycol 300 in guinea-pig atria

Abstract

Polyethylene glycol 300 (PEG 300) elicited a dose-related negative inotropic response in guinea-pig left atria at 37°. However, when the tissue was washed and a second dose-response relationship determined, PEG 300 then elicited a marked positive inotropic response. The positive response was not the result of catecholamine release since it was still observed in reserpine-pretreated as well asin propranolol treated tissues. Atropine, phentolamine and triprolidine had no effect upon this result. PEG 300 had little effect upon dose-response curves to Ca 2+ but in the presence of low ( 1 3 ) Na + solutions, both dose-response curves were negative. The involvement of Na + in the bizarre inotropic responses to PEG 300 was substantiated by the findings that intracellular cardiac action potential amplitudes and the maximal rate of depolarization were markedly depressed while the resting membrane potential amplitude was unchanged. In histochemical studies, PEG 300 (7% v/v) was found to cause a 14 per cent increasc in the activity of Na +, K +-dependent ATPase but did not affect the Mg 2+-activated or mitochondrial Ca 2+-activated ATPases in guinea-pig left atrial strips. Washing the PEG 300 from the tissues caused the enzyme to return to control levels. A second addition of PEG 300 to these tissues did not elicit any changes in the activity of Na +, K +-dependent ATPase. Biochemical studies on isolated enzyme preparations demonstrated that PEG 300 had no direct stimulatory effect upon the activity of Na +, K +-dependent ATPase. It was suggested that PEG 300 increases the number of sites of enzyme activity, similar to deoxycholate treatment.