Effect of norepinephrine and cyclic AMP on intracellular sodium ion activity and contractile force in canine cardiac Purkinje fibers.
The effect of norepinephrine on the Na+-K+ pump was investigated by simultaneously measuring intracellular sodium ion activity (aiNa) and contractile force of canine cardiac Purkinje fibers driven at 1.0 Hz in K+-free solution, high K+ solution, and in the presence of tetrodotoxin. In Tyrode solution containing 5.4mM [K+]o, 10(-6) M norepinephrine decreased aiNa, whereas in K+-free solution 10(-6) M norepinephrine did not lower aiNa. 16.2 mM [K+]o decreased aiNa from 8.8 +/- 0.9 mM to 6.5 +/- 0.5 mM (mean +/- SD, n = 5). Exposure to 10(-6) M norepinephrine in the presence of high [K+]o further decreased aiNa by 0.7 +/- 0.4 mM. This further decrease was prevented by exposure to 2.5 X 10(-6) M strophanthidin (n = 4). Blockade of the fast sodium channel with 5 X 10(-6) M tetrodotoxin lowered aiNa from 8.5 +/- 1.3 mM to 7.4 +/- 1.1 mM (n = 4). Exposure to 10(-6) M norepinephrine in the presence of tetrodotoxin further lowered aiNa by 0.9 +/- 0.2 mM. We also studied the effects of the analogues of adenosine 3':5'-cyclic monophosphate, N6, 2'-0-dibutyryladenosine 3':5'-cyclic monophosphate, and 8-(4-chlorophenylthiol)-adenosine 3':5'-cyclic monophosphate on aiNa and twitch tension. Both analogues lowered to aiNa and increased twitch tension mimicking the effects of norepinephrine. Our results support the hypothesis that norepinephrine lowers aiNa by stimulating the Na+-K+ pump in this tissue. This stimulation appears to be mediated by adenosine 3':5'-cyclic monophosphate and does not appear to be due to intercellular K+ accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D012964:Sodium; D000242:Cyclic AMP; D011188:Potassium; D009638:Norepinephrine