Su Young Han1, Chris P Bolter. 1. Department of Physiology and the Centre for Neuroscience, University of Otago, Dunedin, New Zealand.
Abstract
UNLABELLED: Controversy persists regarding participation of the muscarinic-activated potassium current (c(KACh)) in small and moderate vagal bradycardia. We investigated this by (i) critical examination of earlier experimental data for mechanisms proposed to operate in modest vagal bradycardia (modulation of I(f) and inhibition of a junctional Na(+) current) and (ii) experiments performed on isolated vagally-innervated guinea-pig atria. In 8 superperfused preparations, 10-s trains of vagal stimulation (1 to 20Hz) produced a bradycardia that ranged from 1 to 80%. Hyperpolarisation of sinoatrial cells accompanied bradycardia in 65/67 observations (linear correlation between bradycardia and increase in maximum diastolic potential (mV)=0.076x%; R(2)=0.57; P<0.001). In bath-mounted preparations single supramaximal stimuli to the vagus immediately and briefly increased pacemaker cycle length in 7 of 18 preparations. This response was eliminated by 300nM tertiapin-Q. Trains of 10 single supramaximal vagal stimuli applied at 1-s intervals caused progressive increase in overall cycle length during the train; immediate and brief increases in cycle length occurred following some stimuli. Immediate brief responses and part of the slower response to the stimulus train were removed by 300nM tertiapin-Q. SUMMARY: experimental data shows that small and modest vagal bradycardia is accompanied by hyperpolarisation of the pacemaker cell which is severely attenuated by tertiapin-Q. These observations support the idea that activation of I(KACh) occurs at all levels of vagal bradycardia. Contradictory conclusions from earlier studies may be attributed to the nature of experimental models and experimental design.
UNLABELLED: Controversy persists regarding participation of the muscarinic-activated potassium current (c(KACh)) in small and moderate vagal bradycardia. We investigated this by (i) critical examination of earlier experimental data for mechanisms proposed to operate in modest vagal bradycardia (modulation of I(f) and inhibition of a junctional Na(+) current) and (ii) experiments performed on isolated vagally-innervated guinea-pig atria. In 8 superperfused preparations, 10-s trains of vagal stimulation (1 to 20Hz) produced a bradycardia that ranged from 1 to 80%. Hyperpolarisation of sinoatrial cells accompanied bradycardia in 65/67 observations (linear correlation between bradycardia and increase in maximum diastolic potential (mV)=0.076x%; R(2)=0.57; P<0.001). In bath-mounted preparations single supramaximal stimuli to the vagus immediately and briefly increased pacemaker cycle length in 7 of 18 preparations. This response was eliminated by 300nM tertiapin-Q. Trains of 10 single supramaximal vagal stimuli applied at 1-s intervals caused progressive increase in overall cycle length during the train; immediate and brief increases in cycle length occurred following some stimuli. Immediate brief responses and part of the slower response to the stimulus train were removed by 300nM tertiapin-Q. SUMMARY: experimental data shows that small and modest vagal bradycardia is accompanied by hyperpolarisation of the pacemaker cell which is severely attenuated by tertiapin-Q. These observations support the idea that activation of I(KACh) occurs at all levels of vagal bradycardia. Contradictory conclusions from earlier studies may be attributed to the nature of experimental models and experimental design.