The negative inotropic effect of XXXX on ferret ventricular myocardium.

@entity2701 @entity1617 @entity141 @entity934
1. The effects of @entity934 ( @entity1617 ) on developed @entity2701 and intracellular @entity141 concentration (as measured with aequorin) were studied in ferret papillary muscles, and on twitch shortening, the action potential and membrane currents in ferret ventricular myocytes. 2. Addition of @entity1617 to ferret papillary muscles resulted in decreases in developed @entity2701 and the intracellular @entity141 transient, both of which then partially recovered in the continued presence of @entity1617 ('fade' of the response). On wash-off of @entity1617 both developed @entity2701 and the intracellular @entity141 transient increased above control ('rebound') before returning to control values. 3. Addition of @entity1617 to ferret ventricular myocytes resulted in a membrane hyperpolarization of 2 +/- 0.5 mV (mean +/- S.E.M.; n = 9), a decrease in action potential duration to 23 +/- 6% of control and a decrease in twitch shortening to 31 +/- 5% of control. In the continued presence of @entity1617 these responses to @entity1617 faded. Thirty seconds after the maximal effect of @entity1617 , action potential duration had partially recovered to 34 +/- 6% of control and twitch shortening to 46 +/- 7% of control. 4. The effects of @entity1617 on twitch shortening could be mimicked under voltage clamp by varying voltage clamp pulse duration to simulate the @entity1617 -induced changes in action potential duration. 5. When @entity1617 was applied during a train of voltage clamp pulses of constant duration, 81% of the cells showed less than a 20% decrease in @entity141 current and twitch shortening. However in 19% of the cells twitch shortening and the apparent @entity141 current decreased by more than 30%. 6. In the 81% of cells, the normal decrease in twitch shortening was wholly the result of the shortening of the action potential. This in turn was the result of an increase in an outward background current which increased the rate of repolarization during the action potential. The @entity1617 -induced background current reversed at -89 +/- 2 mV and showed inward-going rectification; these properties suggest that it was carried by K+. 7. In the 19% of cells, the normal decrease in twitch shortening was only partly the result of the shortening of the action potential (due to both the increase in outward background current as well as the apparent decrease in @entity141 current). In these cells the decrease in twitch shortening may also have been partly the direct result of the apparent decrease of @entity141 current.
