Department of Physiology and the Centre for Neuroscience, University of Otago, Dunedin, New Zealand.
Auton Neurosci. 2011 Oct 28;164(1-2):96-100. doi: 10.1016/j.autneu.2011.05.009.
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.
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.
关于毒蕈碱激活的钾电流（c(KACh)）是否参与小而中度迷走性心动过缓仍存在争议。我们通过（i）对先前提出的在中度迷走性心动过缓中起作用的机制的实验数据（调节 I(f)和抑制连接性 Na(+)电流）进行批判性研究，以及（ii）在离体迷走神经支配的豚鼠心房上进行的实验，对此进行了研究。在 8 个超灌注制剂中，1 到 20Hz 的迷走神经刺激 10 秒会产生 1 到 80%的心动过缓。67 次观察中有 65 次（心动过缓与最大舒张电位（mV）增加之间的线性相关性=0.076x%；R(2)=0.57；P<0.001），窦房结细胞的超极化伴随着心动过缓。在浴槽固定制剂中，单次超最大刺激迷走神经立即短暂地增加 7 个制剂中的起搏周期长度。这种反应被 300nM tertiapin-Q 消除。10 个单最大迷走神经刺激以 1 秒的间隔施加 10 个刺激的刺激序列会导致刺激序列期间整体周期长度逐渐增加；在一些刺激后会立即出现短暂的周期长度增加。立即短暂的反应和刺激序列的部分较慢反应被 300nM tertiapin-Q 消除。
实验数据表明，小而中度的迷走性心动过缓伴随着起搏细胞的超极化，这种超极化被 tertiapin-Q 严重削弱。这些观察结果支持了 I(KACh)在所有迷走性心动过缓水平都被激活的观点。早期研究得出的矛盾结论可能归因于实验模型和实验设计的性质。
