Characterization of the effects of Ryanodine, TTX, E-4031 and 4-AP on the sinoatrial and atrioventricular nodes

Nikmaram, M. R.; Liu, Jie; Abdel‐Rahman, Mohamed H.; Dobrzynski, Halina; Boyett, Mark R.; Lei, Ming

doi:10.1016/j.pbiomolbio.2007.07.003

Cited by 32 publications

(52 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AVN myocytes have an intracellular Ca 2ϩ transient, 15 and there is evidence that intracellular Ca 2ϩ may be important in pacemaking in the AVN 16 (as it is in sinoatrial node 17 ). Four Ca 2ϩ -handling proteins were investigated: The ryanodine receptor is the sarcoplasmic reticulum Ca 2ϩ release channel.…”

Section: ؉ -Handling Proteinsmentioning

confidence: 99%

Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis

Greener

Tellez

Dobrzynski

et al. 2009

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

Background-Little is known about the distribution of gap junctions and ion channels in the atrioventricular node, even though the physiology and pathology of the atrioventricular node is ultimately dependent on them. Methods and Results-The abundance of 30 transcripts for markers, gap junctions, ion channels, and Ca 2ϩ -handling proteins in different regions of the rabbit atrioventricular node (nodal extension and proximal and distal penetrating bundle of His as well as atrial and ventricular muscle) was measured using a novel quantitative polymerase chain reaction technique and in situ hybridization. The expression profile of the nodal extension (slow pathway into penetrating bundle) was similar to that of the sinoatrial node. For example, in the nodal extension, in contrast to the atrial muscle and as expected for a slowly conducting tissue with pacemaker activity, there was no or reduced expression of Cx43, Na v 1.5, Ca v 1.2, K v 1.4, KChIP2, and RYR3 and high expression of Ca v 1.3 and HCN4. The expression profile of the penetrating bundle was less specialized. In situ hybridization revealed a transitional zone with reduced expression of Cx43, Na v 1.5, and KChIP2 that may form the fast pathway into the penetrating bundle. Conclusions-At the atrioventricular node, the expression of gap junctions and ion channels in the nodal extension (slow pathway) and a transitional zone (putative fast pathway) as well as the penetrating bundle (output pathway) is specialized and heterogeneous and roughly matches the electrophysiology of the different regions.

show abstract

Section: ؉ -Handling Proteinsmentioning

confidence: 99%

Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis

Greener

Tellez

Dobrzynski

et al. 2009

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, the cellular electrophysiological basis of AVN pacemaking is incompletely understood, though it is clear that this is also likely to involve multiple ionic conductances [6], [7], [8]. For example, in the rabbit intact AVN inhibition of the hyperpolarization activated pacemaker current “I f ” slows but does not stop AVN junctional rhythm [9], [10]; this is consistent with an important though not obligatory role for I f in AVN pacemaking. There is also evidence from both rabbit and dog preparations that intracellular Ca 2 + cycling influences AVN pacemaking rate [11], [12], [13], [14], whilst Cav1.3 and 3.1 have been implicated in mouse AVN pacemaking [8].…”

Section: Introductionmentioning

confidence: 96%

Characterization and influence of cardiac background sodium current in the atrioventricular node

Cheng

James

et al. 2016

Journal of Molecular and Cellular Cardiology

Self Cite

View full text Add to dashboard Cite

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 mM), Gd3 + (100 μM), ruthenium red (100 μM), or amiloride (1 mM) produced modest reductions in IB,Na. Flufenamic acid was without significant effect, whilst La3 + (100 μM) 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.

show abstract

“…Before the discovery of the hyperpolarization-activated current, the diastolic depolarization was thought to result from the decay of an outward K + current (Noble & Tsien, 1968). However, in 1979 this decaying outward current was shown to be an inward current activated upon hyperpolarization (Brown et al, 1979).…”

Section: Hyperpolarization-activated Current (Funny Current I F )mentioning

confidence: 99%

“…+ currents The delayed rectifier K + current (I K ), first described in Purkinje fibers in 1968 (Noble & Tsien, 1968), is composed of three different components: the ultra-rapid (I Kur ), rapid (I Kr ) , and slow (I Ks ) components. Figure 3B, shows typical examples and I-V relationships of the various I K components in rabbit SA node cells.…”

Section: Delayed Rectifier Kmentioning

confidence: 99%

See 1 more Smart Citation

Creation of a Biopacemaker: Lessons from the Sinoatrial Node

Haan¹,

Verkerk

Tan³

2011

Modern Pacemakers - Present and Future

View full text Add to dashboard Cite

Characterization of the effects of Ryanodine, TTX, E-4031 and 4-AP on the sinoatrial and atrioventricular nodes

Cited by 32 publications

References 25 publications

Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis

Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis

Characterization and influence of cardiac background sodium current in the atrioventricular node

Creation of a Biopacemaker: Lessons from the Sinoatrial Node

Contact Info

Product

Resources

About