Evidence map›Paper›PMID 33235894›Full record

ArticleAmerican journal of clinical and experimental urology2020

Constitutively active HCN channels constrain detrusor excitability and modulate evoked contractions of human bladder.

Mahendra Kashyap, Nishant Singh, Naoki Yoshimura, Christopher Chermansky, Pradeep Tyagi

Open access · greenAbstract read
PubMed Full text at PMC
In one paragraph

Article in American journal of clinical and experimental urology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Vascular mechanotransduction.Physiological reviews · 2023
    Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Mahendra KashyapUniversity of Alabama Birmingham, AL, USA.
Nishant SinghDepartment of Urology, University of Pittsburgh Pittsburgh, PA, USA.
Naoki YoshimuraDepartment of Urology, University of Pittsburgh Pittsburgh, PA, USA.
Christopher ChermanskyDepartment of Urology, University of Pittsburgh Pittsburgh, PA, USA.
Pradeep TyagiDepartment of Urology, University of Pittsburgh Pittsburgh, PA, USA.
University of Pittsburgh · USUniversity of Alabama at Birmingham · US

Funding

A Novel Combination Drug Treatment for Detrusor Hyperactivity with Impaired Contractile Function (DHIC)R21AG062971 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TYAGI, PRADEEP · 2019 to 2020
$430k
NIA NIH HHS R21 AG062971
6 · The paper itself

Abstract

objectiveExpression of Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is reported in bladder, but the functional role remains unsettled. Here, we immunolocalized the HCN1 and HCN4 subtype in human bladder and investigated their functional significance.

methodsBladder procured from ten organ donors was dissected into mucosa (containing urothelium and submucosa) and detrusor for double immunofluorescence of HCN1 and 4 subtypes with gap junction and neural proteins together with isometric tension recordings. Mucosa intact and denuded detrusor strips were stretched to a basal tension of 10 mN for eliciting either tetrodotoxin (TTX) resistant spontaneous, carbachol evoked contractions and TTX sensitive electrical field stimulated (EFS), pre and post-addition of HCN blocker, ZD7288 or the activator, Lamotrigine or the cholinesterase inhibitor, Neostigmine.

resultsDouble immunofluorescence revealed immunolocalization of HCN1 and HCN4 subtype with calcitonin gene related peptide (CGRP), choline acetyl transferase and gap junction proteins in mucosa and detrusor. Removal of mucosa significantly raised the resting tension and the force of spontaneous contractions upon cumulative addition of ZD7288 in micromolar range relative to Lamotrigine treated strips (P<0.05). ZD7288 [10 nM] did not affect the contractile response evoked by EFS or carbachol, but the addition of ZD7288 [10 nM] in presence of Neostigmine [1 µM] significantly enhanced the atropine and TTX sensitive EFS evoked contractions of mucosa denuded strips.

conclusionsOverall, HCN channels immunolocalized in mucosa, smooth muscle, gap junctions and nerve fibers exert a tonic constraint on detrusor excitability, enable spatio-temporal integration of evoked contractions and constrain the release of neurotransmitters, respectively. In contrast to the pacemaker role in other organs, findings argue for a non-pacemaking role of HCN channels in human bladder.

Indexed as

carbacholHCN channelsimmunofluorescencelamotriginenerve evoked contractionsspontaneous contractionZD7288

Identifiers

PMID33235894
PMCPMC7677517
OpenAlexW3086658190

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.