What is the clinical evidence from this study?

Study design: Other. Population: Healthy (mouse atria). Intervention: Carbachol (CCh) vs. Control (baseline). Primary outcome: IKACh current density (Right vs Left atrium) (p=<0.05).

October 1, 2003Open Access

Electrophysiological evidence for a gradient of G protein‐gated K+ current in adult mouse atria

Q: What are the key findings of this study?

Right atrial myocytes exhibited significantly higher IKACh current density than left atrial myocytes, and SA node myocytes had higher density than both, revealing a gradient across mouse atria.

Key Result

Right atrial myocytes exhibited significantly higher IKACh current density than left atrial myocytes, and SA node myocytes had higher density than both, revealing a gradient across mouse atria.

PICO

Population

Healthy (mouse atria)

Intervention / Comparator

Carbachol (CCh) vs Control (baseline) (10 µM)

Primary Outcome

IKACh current density (Right vs Left atrium), p=<0.05

Main Result

p-value: p=<0.05

Limitations

Decreases in excitability and action potential duration were observed in response to higher concentrations of muscarinic agonist than are likely to be encountered following normal vagal nerve stimulation in vivo.
Did not measure expression levels of ion channel subunits, G-protein subunits, or interacting intracellular second messengers to identify the underlying cause of the IKACh current gradient.

Abstract

Whole cell current and voltage clamp techniques were used to examine the properties of acetylcholine-sensitive K+ current (IKACh) in myocytes from adult mouse atrium. Superfusion of a maximal dose of carbachol (CCh; 10 microM) caused a substantial increase in K+ current in all myocytes examined. The current-voltage (I-V) relation of maximally activated IKACh exhibited weak inward rectification. Consequently, CCh increased the amount of depolarising current necessary to evoke action potentials (APs), and APs evoked in CCh had significantly shorter durations than control APs (P<0.05). The effects of CCh on K+ current and on AP properties were blocked by the muscarinic receptor antagonist methoctramine (1 microM). ACh (10 microM) activated a K+ current with identical properties to that activated by CCh, as did the A1 receptor agonist adenosine (100 microM). Right atrial myocytes had significantly more IKACh than left atrial myocytes (P<0.05), regardless of whether IKACh was evoked by superfusion of muscarinic or A1 receptor agonists. IKACh current density was significantly higher in SA node myocytes than either right or left atrial myocytes. These data identify a gradient of IKACh current density across the supraventricular structures of mouse heart. This gradient, combined with the heterogeneous distribution of parasympathetic innervation of the atria, may contribute to the proarrhythmic ability of vagal nerve stimulation to augment dispersion of atrial refractoriness.

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Cite This Study

Lomax et al. (Wed,) conducted a other in Healthy (mouse atria). Carbachol (CCh) vs. Control (baseline) was evaluated on IKACh current density (Right vs Left atrium) (p=<0.05). Right atrial myocytes exhibited significantly higher IKACh current density than left atrial myocytes, and SA node myocytes had higher density than both, revealing a gradient across mouse atria.

synapsesocial.com/papers/6a1c870ce2119f9cbea16f28 https://doi.org/https://doi.org/10.1038/sj.bjp.0705474