Tertiapin-Q removes a large and rapidly acting component of vagal slowing of the guinea-pig cardiac pacemaker.
The participation of acetylcholine-activated potassium current (I(K,ACh)) and hyperpolarization-activated pacemaker current (I(f)) in vagal bradycardia were examined using vagally-innervated preparations of guinea-pig atria. Preparations were maintained in Krebs-Henseleit solution (36 degrees C). Before treatment, trains of vagal stimuli (10 s at 2, 5 and 10 Hz) produced graded bradycardias displaying rapid onset and offset. Tertiapin-Q (300 nM), which blocks I(K,ACh), had no effect on baseline atrial rate. In tertiapin-Q, vagal bradycardia displayed a gradual onset and offset, with a peak response ~50% of that recorded in control conditions. Cumulative addition of 1 mM ZD7288 (blocker of I(f)) caused atrial rate to fall by ~60%, but had no further effect on the amplitude of the vagal bradycardia, while response onset and offset became slightly faster. From these observations, we argue that (i) vagal bradycardia was attributable primarily to activation of I(K,ACh), (ii) vagal modulation of I(f) had a minor influence on the rate of onset and offset of bradycardia, and (iii) removal of the influence of I(K,ACh) unmasked a slow response, of undetermined origin, to vagal stimulation. In a separate set of experiments we compared the effects of 1 mM Ba(2+) and 300 nM tertiapin-Q on vagal bradycardia. Ba(2+) reduced baseline atrial rate and the response to vagal stimulation. Subsequent cumulative addition of tertiapin-Q had no additional effect on baseline atrial rate, but caused further reduction in the amplitude of vagal bradycardia, suggesting that 1 mM Ba(2+) did not achieve a complete block of I(K,ACh) in this preparation.
Bolter
Chris P
CP
Department of Physiology and the Centre for Neuroscience, University of Otago, Dunedin, New Zealand. chris.bolter@stonebow.otago.ac.nz
Turner
Michael J
MJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010138:Pacemaker, Artificial; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
D017609:Barium Compounds; D001514:Bee Venoms; D002317:Cardiovascular Agents; D002712:Chlorides; D026902:Potassium Channel Blockers; D011743:Pyrimidines; C024986:barium chloride; C082246:ICI D2788; C029738:tertiapin