| Budget Amount *help |
¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Outline of Final Research Achievements |
The heart rate is dynamically controlled by the autonomic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are well-known molecular marker of SAN, although its physiological role still remains matter of debate. We therefore developed novel transgenic mice in which expression level of HCN4 channels could be reversibly changed from zero to ~3 times of that in wild type mice, using tetracycline trans-activator and tetracycline responsive element. We found that overexpression of HCN4 channels reduced the parasympathetic response of SAN, whereas genetic silencing of HCN4 channels generated opposite phenotypic changes. Our study suggested that HCN4 channels attenuate the vagal response of SAN, and prevent excessive bradycardia. We concluded that HCN4 channels maintain the heart rate variability within a physiological range by this mechanism.
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