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.
Tripathi
O
O
Department of Pharmacology, Central Drug Research Institute, Lucknow, India.
Ray
M
M
Bajpai
V K
VK
Bhatnagar
A
A
Kumar
R
R
Singh
Y K
YK
Singh
C
C
Shipstone
A C
AC
Dhawan
B N
BN
D000200:Action Potentials; D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000648:ultrastructure; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology
D003840:Deoxycholic Acid; D001285:Atropine; D007545:Isoproterenol; D009638:Norepinephrine