Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice

10.3791/62735 ◽  
2021 ◽  
Author(s):  
Praveen Kumar ◽  
Man Si ◽  
Kelsey Paulhus ◽  
Edward Glasscock
Keyword(s):  
Firing Rate ◽  
Microelectrode Array ◽  
Sinoatrial Node ◽  
Cardiac Pacemaking

scholarly journals Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis

2021 ◽  
Vol 8 (4) ◽  
pp. 40
Author(s):  
Marietta Easterling ◽  
Simone Rossi ◽  
Anthony J Mazzella ◽  
Michael Bressan
Keyword(s):  
Cardiac Tissue ◽  
Sinoatrial Node ◽  
Cardiac Pacemaker ◽  
Tissue Level ◽  
Rhythmic Contraction ◽  
Entire Volume ◽  
Impulse Generation ◽  
Cardiac Pacemaking ◽  
Electrical Impulses ◽  
Sufficient Strength

Cardiac pacemaker cells located in the sinoatrial node initiate the electrical impulses that drive rhythmic contraction of the heart. The sinoatrial node accounts for only a small proportion of the total mass of the heart yet must produce a stimulus of sufficient strength to stimulate the entire volume of downstream cardiac tissue. This requires balancing a delicate set of electrical interactions both within the sinoatrial node and with the downstream working myocardium. Understanding the fundamental features of these interactions is critical for defining vulnerabilities that arise in human arrhythmic disease and may provide insight towards the design and implementation of the next generation of potential cellular-based cardiac therapeutics. Here, we discuss physiological conditions that influence electrical impulse generation and propagation in the sinoatrial node and describe developmental events that construct the tissue-level architecture that appears necessary for sinoatrial node function.

scholarly journals SK4 Ca 2+ -Activated K + Channels Regulate Sinoatrial Node Firing Rate and Cardiac Pacing In Vivo

2017 ◽  
Vol 112 (3) ◽  
pp. 35a ◽  
Author(s):  
Bernard Attali ◽  
David Weisbrod ◽  
Hanna Bueno ◽  
Joachim Behar ◽  
Shiraz Haron-Khun ◽  
...  
Keyword(s):  
Firing Rate ◽  
Sinoatrial Node ◽  
Cardiac Pacing ◽  
K Channels

scholarly journals STIM1–Ca2+ signaling modulates automaticity of the mouse sinoatrial node

2015 ◽  
Vol 112 (41) ◽  
pp. E5618-E5627 ◽  
Author(s):  
Hengtao Zhang ◽  
Albert Y. Sun ◽  
Jong J. Kim ◽  
Victoria Graham ◽  
Elizabeth A. Finch ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Membrane Surface ◽  
Surface Membrane ◽  
Autonomic Response ◽  
Sinus Arrest ◽  
Cholinergic Signaling ◽  
Ionic Fluxes ◽  
Cardiac Pacemaking ◽  
Specific Deletion

Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on the membrane surface (membrane clock) with rhythmic Ca2+ release from internal Ca2+ stores (Ca2+ clock) to adjust heart rate to meet hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1) and Orai1 channels, key components of store-operated Ca2+ entry, are selectively expressed in SANCs. Cardiac-specific deletion of STIM1 in mice resulted in depletion of sarcoplasmic reticulum (SR) Ca2+ stores of SANCs and led to SAN dysfunction, as was evident by a reduction in heart rate, sinus arrest, and an exaggerated autonomic response to cholinergic signaling. Moreover, STIM1 influenced SAN function by regulating ionic fluxes in SANCs, including activation of a store-operated Ca2+ current, a reduction in L-type Ca2+ current, and enhancing the activities of Na+/Ca2+ exchanger. In conclusion, these studies reveal that STIM1 is a multifunctional regulator of Ca2+ dynamics in SANCs that links SR Ca2+ store content with electrical events occurring in the plasma membrane, thereby contributing to automaticity of the SAN.

scholarly journals Cyclic AMP reverses the effects of aging on pacemaker activity and If in sinoatrial node myocytes

2017 ◽  
Vol 149 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Emily J. Sharpe ◽  
Eric D. Larson ◽  
Catherine Proenza
Keyword(s):  
Cyclic Amp ◽  
Firing Rate ◽  
Sinoatrial Node ◽  
Voltage Dependence ◽  
Pacemaker Activity ◽  
Firing Rates ◽  
Aged Mice ◽  
Age Dependent ◽  
Effects Of Aging ◽  
Hyperpolarizing Shift

Aerobic capacity decreases with age, in part because of an age-dependent decline in maximum heart rate (mHR) and a reduction in the intrinsic pacemaker activity of the sinoatrial node of the heart. Isolated sinoatrial node myocytes (SAMs) from aged mice have slower spontaneous action potential (AP) firing rates and a hyperpolarizing shift in the voltage dependence of activation of the “funny current,” If. Cyclic AMP (cAMP) is a critical modulator of both AP firing rate and If in SAMs. Here, we test the ability of endogenous and exogenous cAMP to overcome age-dependent changes in acutely isolated murine SAMs. We found that maximal stimulation of endogenous cAMP with 3-isobutyl-1-methylxanthine (IBMX) and forskolin significantly increased AP firing rate and depolarized the voltage dependence of activation of If in SAMs from both young and aged mice. However, these changes were insufficient to overcome the deficits in aged SAMs, and significant age-dependent differences in AP firing rate and If persisted in the presence of IBMX and forskolin. In contrast, the effects of aging on SAMs were completely abolished by a high concentration of exogenous cAMP, which restored AP firing rate and If activation to youthful levels in cells from aged animals. Interestingly, the age-dependent differences in AP firing rates and If were similar in whole-cell and perforated-patch recordings, and the hyperpolarizing shift in If persisted in excised inside-out patches, suggesting a limited role for cAMP in causing these changes. Collectively, the data indicate that aging does not impose an absolute limit on pacemaker activity and that it does not act by simply reducing the concentration of freely diffusible cAMP in SAMs.

Cardiac pacemaking in the sinoatrial node

1993 ◽  
Vol 73 (1) ◽  
pp. 197-227 ◽  
Author(s):  
H. Irisawa ◽  
H. F. Brown ◽  
W. Giles
Keyword(s):  
Sinoatrial Node ◽  
Cardiac Pacemaking

Abstract 12655: Cardiac Pacing Alters Neural Information Processing in the Intrinsic Cardiac Nervous System

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pradeep S Rajendran ◽  
Marmar Vaseghi ◽  
J Andrew Armour ◽  
Jeffrey L Ardell ◽  
Kalyanam Shivkumar
Keyword(s):  
Nervous System ◽  
Information Processing ◽  
Firing Rate ◽  
Microelectrode Array ◽  
Cardiac Pacing ◽  
Left Ventricular ◽  
Right Atrial ◽  
Dependent Effect ◽  
Basal Activity ◽  
Significant Difference

Introduction: Cardiac pacing is an established therapy; however, it may have detrimental effects on cardiac neurohumoral control. We investigated the effects of pacing on the intrinsic cardiac nervous system (ICNS), an important coordinator of regional cardiac function. Methods: Activity from intrinsic cardiac (IC) neurons in the ventral interventricular ganglionated plexus (VIV GP) was recorded using a linear microelectrode array in 5 normal pigs. Changes in IC activity were evaluated in response to epicardial pacing (current: 6 mA; pulse width: 2 ms) at 10% above resting heart rate at the following sites: (1) right atrial appendage (RAA), (2) right ventricular (RV) apex, and (3) left ventricular (LV) posterolateral wall. Results: A total of 72 IC neurons were identified. The proportion of neurons responding to pacing was 23% at RAA, 27% at RV apex, and 27% at LV posterolateral wall. Pacing at each site caused significant activation (p < 0.01), significant suppression (p < 0.01), or no change in firing rate of different subsets of neurons. Of all sites, the largest change in firing rate from basal activity was at the LV posterolateral wall, with a significant increase of 1.38 Hz (p < 0.01) in neurons activated by pacing and a significant decrease of 0.63 Hz (p < 0.01) in those suppressed by pacing (Figure 1). There was also a significant difference in basal activity between neurons activated by pacing versus those suppressed by pacing (p < 0.01). Conclusions: Our results suggest that pacing has a site-dependent effect on the ICNS. We observed effects with both atrial and ventricular pacing and that LV posterolateral pacing has the greatest impact on neural activity in the VIV GP. Also, neurons with low levels of basal activity tended to be activated by pacing, and those with high levels of basal activity tended to be suppressed, indicating a state-dependent effect. Modulation of information processing in the ICNS may provide the link between pacing and neuroendocrine activation.

Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model

1999 ◽  
Vol 276 (6) ◽  
pp. H2221-H2244 ◽  
Author(s):  
Semahat S. Demir ◽  
John W. Clark ◽  
Wayne R. Giles
Keyword(s):  
Sinoatrial Node ◽  
Vagal Stimulation ◽  
Full Range ◽  
Rabbit Heart ◽  
Pacemaker Activity ◽  
Membrane Hyperpolarization ◽  
Different Types ◽  
Cardiac Pacemaking ◽  
Rabbit Sinoatrial Node ◽  
Diastolic Potential

We have extended our compartmental model [ Am. J. Physiol. 266 ( Cell Physiol. 35): C832–C852, 1994] of the single rabbit sinoatrial node (SAN) cell so that it can simulate cellular responses to bath applications of ACh and isoprenaline as well as the effects of neuronally released ACh. The model employs three different types of muscarinic receptors to explain the variety of responses observed in mammalian cardiac pacemaking cells subjected to vagal stimulation. The response of greatest interest is the ACh-sensitive change in cycle length that is not accompanied by a change in action potential duration or repolarization or hyperpolarization of the maximum diastolic potential. In this case, an ACh-sensitive K+ current is not involved. Membrane hyperpolarization occurs in response to much higher levels of vagal stimulation, and this response is also mimicked by the model. Here, an ACh-sensitive K+ current is involved. The well-known phase-resetting response of the SAN cell to single and periodically applied vagal bursts of impulses is also simulated in the presence and absence of the β-agonist isoprenaline. Finally, the responses of the SAN cell to longer continuous trains of periodic vagal stimulation are simulated, and this can result in the complete cessation of pacemaking. Therefore, this model is 1) applicable over the full range of intensity and pattern of vagal input and 2) can offer biophysically based explanations for many of the phenomena associated with the autonomic control of cardiac pacemaking.

Sign in / Sign up

Export Citation Format

Share Document