Effects of @entity6743 on the mechanical and electrical activities and ultrastructure of XXXX atria.

@entity6743 @entity71086 @entity840 @entity3044 @entity3897 @entity141 @entity2483 @entity1063 @entity4420
The mechanism of cardio-inhibitory effects of @entity6743 ( @entity4420 ) was investigated by studying its effects on the contractility, action potentials (APs) and ultrastructure of @entity840 atrial preparations. @entity4420 (10(-7)-10(-4) M) caused reversible negative ino- (NIE) and chrono-tropy in spontaneously beating (SBA) and NIE in electrically driven left ( @entity71086 ) atria. At higher doses (greater than or equal to 1.10(-3) M) @entity4420 caused irreversible inhibition of contractions. @entity3897 (10(-7)-10(-4) M) failed to inhibit both the reversible and irreversible effects of @entity4420 . The NIE due to lower doses of @entity4420 (less than or equal to 1.10(-4) M) was inhibited by higher [ @entity141 ]0, @entity3044 (10(-6)-10(-4) M), and @entity1063 (10(-6)-10(-5) M), which did not alter the dose of @entity4420 required for the irreversible and complete NIE. In lower doses (10(-7)-10(-4) M) @entity4420 caused a reversible inhibition of the AP durations at -20 and -40 mV (APD20 and APD40, respectively), but increased the AP duration at 90% repolarisation (APD90). At higher doses (greater than 5.10(-4) M) it caused an irreversible membrane depolarization, reduction in APD20 and APD40, and complete cessation of electrical activity. The ultrastructural changes in atria treated with 1.10(-4) M @entity4420 were characterized by poorly delineated glycocalyx and at greater than 1.10(-3) M by disruption of sarcolemma and sarcoplasmic reticulum and swelling disruption of mitochondria. Taken together these observations show that @entity4420 caused reversible and irreversible inhibition of atrial contractions at low (10(-7)-10(-4) M) and high (greater than 5.10(-4) M) concentrations, respectively, by different mechanisms. The former effect is due to inhibition of @entity141 channel activity and the latter due to its detergent property causing @entity2483 .
