Analysis Tools
cardiovascular system
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• unrestrained, conscious homozygous null mice were viable, lacked the cardiac muscarinic-gated potassium channel (IKACh), and displayed a normal mean resting heart rate relative to wild-type
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• at rest, wild-type mice often displayed episodes of mild bradycardia with rapid onset lasting 5-10 s; in contrast, mutant mice failed to adjust heart rate on a rapid time scale (<2 s), with the exception of fast (2-4 Hz) oscillations of low amplitude (1-2 ms)
• mutant mice were unable to alter heart rate significantly on a beat-to-beat time scale, and had much lower heart rate variability (HRV) at frequencies above 0.4 Hz relative to wild-type
• the difference in HRV became pronounced after vagal stimulation with methoxamine
• mutants exhibited a diminished bradycardic response to CCPA and methoxamine (that is, indirect vagal stimulation and A1 adenosine receptor activation, respectively)
• atropine (parasympathetic blockade) failed to reduce the HRV of wild-type mice to the level observed in mutant mice, suggesting that in wild-type mice at rest, the muscarinic-gated atrial potassium is also regulated by nonmuscarinic agonists
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