Cardiac vagal control in a knock-in mouse model of dilated cardiomyopathy with a troponin mutation

Dong-Yun Zhan, Cheng-Kun Du, Tsuyoshi Akiyama, Sachio Morimoto, Shuji Shimizu, Toru Kawada, Mikiyasu Shirai, James T. Pearson

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


The aim of this study was to evaluate cardiac vagal nerve activity and identify the abnormality of cardiac vagal control in heart failure caused by dilated cardiomyopathy (DCM) using a knock-in mouse model with a ΔK210 mutation in the cardiac troponin T gene. The effects of electrical stimulation of the cervical vagal nerve at 5 and 10 Hz (peripheral vagal control) and α2-adrennoceptor stimulation by intravenous medetomidine at 0.1 mg/kg (central vagal control) were examined in wild-type (WT) mice and DCM mice. Microdialysis technique was applied to the left ventricular myocardium of anesthetized mice and myocardial interstitial acetylcholine (ACh) levels were measured by HPLC as an index of ACh release from cardiac vagal nerve endings. Electrical vagal nerve stimulation increased cardiac interval and myocardial interstitial ACh level in both WT and DCM mice, and these responses did not differ between WT and DCM mice. In contrast, intravenous medetomidine increased cardiac interval and myocardial interstitial ACh level in both WT and DCM mice, but the responses of cardiac interval and myocardial interstitial ACh level were significantly suppressed in DCM mice compared to WT mice. Medetomidine did not affect the myocardial interstitial ACh response induced by vagal nerve stimulation in WT mice. In this mouse model of DCM, peripheral vagal control including ACh release from vagal nerve endings and the postsynaptic response of pacemaker cells was preserved, but central vagal control through α2-adrenoceptors was impaired.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalAutonomic Neuroscience: Basic and Clinical
Publication statusPublished - 1 Jul 2017
Externally publishedYes


  • Acetylcholine
  • Cardiac microdialysis
  • Dilated cardiomyopathy
  • Heart failure
  • Medetomidine

Cite this