1. Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype
- Author
-
Nishant Singh, Irina Zabbarova, Youko Ikeda, Anthony Kanai, Christopher Chermansky, Naoki Yoshimura, and Pradeep Tyagi
- Subjects
Male ,Aging ,Potassium Channels ,Urinary Bladder ,General Medicine ,General Biochemistry, Genetics and Molecular Biology ,Rats, Inbred F344 ,Article ,Rats ,Gene Expression Regulation ,Urinary Bladder, Underactive ,Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ,Animals ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
OBJECTIVE: To assess the functional role of Hyperpolarization-activated cyclic nucleotide-gated gated channel (HCN) subtypes in the aging bladder phenotype characterized by diminished bladder volume sensation (BVS) with or without the detrusor instability (DI). METHODS: Expression of HCN subtypes was examined by quantitative RT-PCR and Western blot in aged male Fisher 344 rats (n=15) and young rats (n=15). Nocturnal urination and awake cystometry (CMG) were assessed in presence and absence of a steady state HCN channel blockade achieved with daily oral gavage of vehicle or Ivabradine (HCN blocker) 6mg/kg for 7 days. RESULTS: The association of BVS with the age-related downregulation (~30%) of cAMP sensitive HCN1, HCN2 subtypes, and (~50%) upregulation of cAMP insensitive HCN3 subtype is evinced by a doubling in the mean urine volume of nocturnal voids (0.82 ±0.22 mL vs 0.41 ±0.12 mL; n=10; p < 0.05) predicting an age-related rise in micturition volume threshold (p
- Published
- 2021