Age-related down-regulation of HCN channels in rat sinoatrial node

Huang, Xin; Yang, Pei; Du, Yan; Zhang, Junbo; Ma, Aiqun

doi:10.1007/s00395-007-0660-5

Cited by 52 publications

(48 citation statements)

References 29 publications

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“…Hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs) are responsible for the pacemaker current (I f ) in SAN cells, and remodeling of the I f can lead to SAN dysfunction (6,25). In an animal study, HF downregulated the expression of the HCN subunit of SANs, which may be responsible for SAN dysfunction (6).…”

Section: Discussionmentioning

confidence: 99%

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Chang

Chuang

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0.3 or 3 µM), a sarcoplasmic reticulum Ca 2+ release inhibitor (ryanodine; 0.3 or 3 µM), a sodium current inhibitor (tetrodotoxin; 1, 3 or 10 µM) and a late sodium current inhibitor (ranolazine; 10 µM). Western blot analysis was used to investigate the protein expression in SANs from normal rabbits and those with HF. Control SANs had a higher beating rate than SANs from rabbits with HF (2.3±0.1 vs. 1.5±0.1 Hz; P<0.001). Similarly, ivabradine (10 µM), KN-93 (3 µM), ranolazine (10 µM) and ryanodine (3 µM) decreased the beating rates of SANs in the control (n=6) and HF (n=6) groups. Ivabradine treatment resulted in a higher incidence of AP block in HF vs. control SANs (66.7 vs. 0%; P<0.05). Tetrodotoxin (1, 3 or 10 µM) decreased the beating rate to a higher extent in SANs from rabbits with HF than in those from control rabbits and induced a higher incidence of AP block (66.7 vs. 0%; P<0.05). Furthermore, SANs from rabbits with HF had higher protein levels of phospholamban (PLB) and lower levels of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, ryanodine receptor and phosphorylated PLB than control SANs. In conclusion, HF modulates electropharmacological responses in the SAN by channel regulation, which may result in SAN dysfunction.

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Section: Discussionmentioning

confidence: 99%

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Chang

Chuang

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…In rats, an age-dependent decrease in HCN1, 29 HCN2, and HCN4 transcription has been observed. 30 The effect of Cs + on pacemaker activity was consistently reduced with age. Because aging is associated with deteriorating SAN function, the transcription and relative function of HCN channels may contribute to the decline of function in aged rats.…”

Section: Expression Patterns Of Hcn Channelsmentioning

confidence: 98%

New Therapeutic Targets in Cardiology

Roubille

Tardif

2013

Circulation

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“…In the present study, no age-related change in HCN4 was detected (cf. Huang et al 2007). The age-dependent increase in TASK1 in the SAN discussed above could also contribute.…”

Section: Age-dependent Decrease In Ihrmentioning

confidence: 99%

Ageing-dependent remodelling of ion channel and Ca²⁺clock genes underlying sino-atrial node pacemaking

Tellez

Mączewski

Yanni

et al. 2011

Experimental Physiology

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The function of the sino-atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age-dependent decrease in the Ca 2+ clock gene, RYR2, and changes in many ion channels (e.g. increases in Na v 1.5, Na v β1 and Ca v 1.2 and decreases in K v 1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca 2+clock genes in the SAN, and the changes may provide a partial explanation for the age-dependent decline in pacemaker function.

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Age-related down-regulation of HCN channels in rat sinoatrial node

Cited by 52 publications

References 29 publications

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

New Therapeutic Targets in Cardiology

Ageing-dependent remodelling of ion channel and Ca²⁺clock genes underlying sino-atrial node pacemaking

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Age-related down-regulation of HCN channels in rat sinoatrial node

Cited by 52 publications

References 29 publications

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

New Therapeutic Targets in Cardiology

Ageing-dependent remodelling of ion channel and Ca2+clock genes underlying sino-atrial node pacemaking

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Ageing-dependent remodelling of ion channel and Ca²⁺clock genes underlying sino-atrial node pacemaking