Effects of sodium deoxycholate on the mechanical and electrical activities and ultrastructure of guinea pig atria.

The mechanism of cardio-inhibitory effects of sodium deoxycholate (DOC) was investigated by studying its effects on the contractility, action potentials (APs) and ultrastructure of guinea pig atrial preparations. DOC (10(-7)-10(-4) M) caused reversible negative ino- (NIE) and chrono-tropy in spontaneously beating (SBA) and NIE in electrically driven left (EDA) atria. At higher doses (greater than or equal to 1.10(-3) M) DOC caused irreversible inhibition of contractions. Atropine (10(-7)-10(-4) M) failed to inhibit both the reversible and irreversible effects of DOC. The NIE due to lower doses of DOC (less than or equal to 1.10(-4) M) was inhibited by higher [Ca2+]0, isoprenaline (10(-6)-10(-4) M), and noradrenaline (10(-6)-10(-5) M), which did not alter the dose of DOC required for the irreversible and complete NIE. In lower doses (10(-7)-10(-4) M) DOC 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 DOC 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 DOC 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 Ca2+ channel activity and the latter due to its detergent property causing removal of subcellular components.