Bisoprolol reversed small conductance calcium-activated potassium channel (SK) remodeling in a volume-overload rat model.

Abstract

A recent study indicated that apamin-sensitive current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) density significantly increased in heart failure and led to recurrent spontaneous ventricular fibrillation. While the underlying molecular correlation with SK channels is still undetermined, we hypothesized that they are remodeled in HF and that bisoprolol could reverse the remodeling. Volume-overload models were created on male Sprague-Dawley rats by producing an abdominal arteriovenous fistula. Confocal microscopy, quantitative real-time PCR, and western blot were performed to investigate the expression of SK channels and observe the influence of β-blocker bisoprolol on the expression of SK channels I KAS, and the effect of bisoprolol on I KAS and the sensitivity of I KAS to [Ca(2+)]i at single isolated cells were also explored using whole-cell patch clamp techniques. SK channels were remodeled in HF rats, displaying the significant increase of SK1 and SK3 channel expression. After the treatment of HF rats with bisoprolol, the expression of SK1 and SK3 channels was significantly downregulated, and bisoprolol effectively downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i. Our data indicated that the expression of SK1 and SK3 increased in HF. Bisoprolol effectively attenuated the change and downregulated I KAS density as well as the sensitivity of I KAS to [Ca(2+)]i.

• Authors: Yajuan Ni, Tingzhong Wang, Xiaozhen Zhuo, Bingxue Song, Jing Zhang, Feng Wei, Hongyuan Bai, Xuehui Wang, Dandan Yang, Li Gao, Aiqun Ma
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 384 Issue 1-2 Pg. 95-103 (Dec 2013) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 23975505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-1 Receptor Antagonists
• Kcnn1 protein, rat
• Kcnn3 protein, rat
• Small-Conductance Calcium-Activated Potassium Channels
• Apamin
• Bisoprolol

Topics

• Adrenergic beta-1 Receptor Antagonists (pharmacology)
• Animals
• Apamin (pharmacology)
• Arteriovenous Fistula
• Bisoprolol (pharmacology)
• Cells, Cultured
• Down-Regulation
• Heart Failure (metabolism)
• Male
• Membrane Potentials (drug effects)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Small-Conductance Calcium-Activated Potassium Channels (biosynthesis, metabolism)
• Ventricular Fibrillation (metabolism)