Reduced expression of HCN channels in the sinoatrial node of streptozotocin-induced diabetic rats.
Diabetes mellitus (DM) is associated with an electrical remodeling of the heart, increasing the risk of arrhythmias. However, knowledge of electrical remodeling in the sinoatrial node (SAN) by DM is limited. We investigated the expression of HCN channel isoforms, HCN1-HCN4, in SAN from streptozotocin (STZ)-induced diabetic rats and the age-matched controls. We found that the STZ-induced diabetic rats have a lower intrinsic heart rate, a lengthened sinoatrial conduction time, and rate-corrected maximal sinoatrial node recovery time in vivo as well as a longer cycle length (CL) in vitro, as compared with the control. Optical mapping of the SAN demonstrated an inferior leading pacemaker site, reduced SAN conduction velocity and diastolic depolarization slope, and a longer action potential duration in the STZ-induced diabetic rats than in the control. The transcripts and proteins of HCN2 and HCN4 in diabetic SAN were reduced. Specific blockade of HCN channels by 3 μmol/L ivabradine significantly prolonged the CL of a Langendorff heart by 18% in the diabetic rats and 26% in the control. The reduced expression of HCN channel isoforms in the SAN of the STZ-induced diabetic rat may be an important contributor to the reduced SAN function in DM.
a Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, 710061.
Xin
X
Huang
b Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, P.R. China, 710068.
Nier
N
Zhong
c School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, 710049.
Hong
H
Zhang
a Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, 710061.
Aiqun
A
Ma
a Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, 710061.
Zuyi
Z
Yuan
a Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, 710061.
Ning
N
Guo
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics* / Q000378:metabolism*; D000077550:Ivabradine; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
D001552:Benzazepines; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D020033:Protein Isoforms; D000077550:Ivabradine
HCN channels; canaux HCN; diabète provoqué par la streptozotocine; dysfonctionnement du nœud sinusal; nœud sinusal; sinoatrial node; sinoatrial node dysfunction; streptozotocin-induced diabetes