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Abstract
Background inward sodium current (IB,Na) that influences
cardiac pacemaking has been comparatively under-investigated. The aim of
this study was to determine for the first time the properties and role
of IB,Na in cells from the heart's secondary pacemaker, the
atrioventricular node (AVN). Myocytes were isolated from the AVN of
adult male rabbits and mice using mechanical and enzymatic dispersion.
Background current was measured using whole-cell patch clamp and
monovalent ion substitution with major voltage- and time-dependent
conductances inhibited. In the absence of a selective pharmacological
inhibitor of IB,Na, computer modelling was used to assess the physiological contribution of IB,Na. Net background current during voltage ramps was linear, reversing close to 0 mV. Switching between Tris- and Na+-containing extracellular solution in rabbit and mouse AVN cells revealed an inward IB,Na,
with an increase in slope conductance in rabbit cells at − 50 mV from
0.54 ± 0.03 to 0.91 ± 0.05 nS (mean ± SEM; n = 61 cells). IB,Na magnitude varied in proportion to [Na+]o. Other monovalent cations could substitute for Na+ (Rb+ > K+ > Cs+ > Na+ > Li+). The single-channel conductance with Na+ as charge carrier estimated from noise-analysis was 3.2 ± 1.2 pS (n = 6). Ni2 + (10 mmol/L), Gd3 + (100 μmol/L), ruthenium red (100 μmol/L), or amiloride (1 mmol/L) produced modest reductions in IB,Na. Flufenamic acid was without significant effect, whilst La3 +
(100 μmol/L) or extracellular acidosis (pH 6.3) inhibited the current
by > 60%. Under the conditions of our AVN cell simulations, removal
of IB,Na arrested spontaneous activity and, in a simulated 1D-strand, reduced conduction velocity by ~ 20%. IB,Na
is carried by distinct low conductance monovalent non-selective cation
channels and can influence AVN spontaneous activity and conduction.
Original language | English |
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Pages (from-to) | 114-124 |
Number of pages | 11 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 97 |
Early online date | 28 Apr 2016 |
DOIs | |
Publication status | Published - 1 Aug 2016 |
Keywords
- Atrioventricular node
- AVN
- Background current
- IB,Na
- Pacemaking
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Dive into the research topics of 'Characterization and influence of cardiac background sodium current in the atrioventricular node'. Together they form a unique fingerprint.Projects
- 1 Finished
-
IP3 receptor modulation of the atrioventricular node
Hancox, J. C. (Principal Investigator)
1/10/14 → 1/10/16
Project: Research
Profiles
-
Professor Jules C Hancox
- School of Physiology, Pharmacology & Neuroscience - Professor of Cardiac Electrophysiology
Person: Academic