MP42-01 QUANTITATIVE STUDY OF INWARD RECTIFYING ION CHANNEL IN DETRUSOR INSTABILITY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2017MP42-01 QUANTITATIVE STUDY OF INWARD RECTIFYING ION CHANNEL IN DETRUSOR INSTABILITY Chitaranjan Mahapatra and Rohit Manchanda Chitaranjan MahapatraChitaranjan Mahapatra More articles by this author and Rohit ManchandaRohit Manchanda More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1290AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Detrusor instability is characterized by sudden involuntary contraction of the detrusor smooth muscle (DSM) cells. In various smooth muscle cells, inward rectifying channel Ih has been playing an important role in regulating resting membrane potential (RMP) and basal tone. Therefore, a detailed biophysical study of Ih channel is essential to investigate DSM cell′s excitability towards detrusor instability. This current study aims to model Ih channel in DSM cells to analyze its′ modulating effects in internal spontaneous myogenic electrical activities. METHODS The DSM cell membrane is represented as a parallel resistor-capacitor circuit consisting of a membrane capacitance Cm and a variable Ih ion channel conductance gh. The voltage-gated Ca2+ and K+ channels, Ca2+ activated K+ channels and leakage currents are incorporated from a published model to generate electrical activities. In this model, Hodgkin-Huxley formalism is adapted for Ih ionic currents with parameters from literature. RESULTS The RMP is set at -50 mV to mimic the experimental value in mouse DSM cell. The maximum conductance of Ih channel is set at 0.0002 mho/cm2 to generate the action potential (AP) shown in figure (Blue line) by inducing synaptic input to mimic effects of purinergic neurotransmitter. By reducing the maximum conductance to 0.00016 mho/cm2, DSM cell couldn′t generate any AP (black line in figure) as the cell is unable to open transient Ca2+ channels. However, higher activation time constant causes the AP (red line) with the higher peak and slower after hyperpolarization compared to control AP (blue line). The AP (red line) is generated early due to faster activation and early crossing of the threshold value. CONCLUSIONS The reduction of Ih channel conductance and activation time constant result hyperpolarization, slower afterhyperpolarization and a consequent reduction in DSM cell′s excitability. Presently, researchers are focusing much effort on developing novel compounds acting through different ways to minimize the severe side effects of anticholinergic agents like trospium chloride and oxybutynin. As the Ih channel blockers hyperpolarize the DSM cell, the pharmacological targeting of these channels may play a dominant role for treatment of detrusor instability. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e544 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Chitaranjan Mahapatra More articles by this author Rohit Manchanda More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...