scholarly journals Spontaneous electrical activity of guinea-pig sinoatrial cells under modulation of two different pacemaker mechanisms

2014 ◽  
Vol 87 (1) ◽  
Author(s):  
Francesca Cacciani ◽  
Massimiliano Zaniboni
Keyword(s):  
Guinea Pig ◽  
Cycle Length ◽  
Calcium Transient ◽  
Similar Degree ◽  
Relative Role ◽  
Pacemaker Cells ◽  
Inward Current ◽  
Cationic Current ◽  
Diastolic Depolarization ◽  
Cardiac Automaticity

The main cellular determinants of cardiac automaticity are the hyperpolarization-activated cationic current If, and the electrogenic Na+/Ca2+ exchanger which generates an inward current after each action potential (AP). Our goal was to evaluate their relative role in pacemaking, by means of application of Ivabradine (IVA) (specific If blocker) and Ryanodine (RYA) (known to abolish calcium transient) on enzimatically isolated guinea-pig pacemaker cells. Spontaneous APs were recorded in patch-clamp whole cell configuration at 36°C from 7 cells perfused with the following sequence of solutions: physiological normal tyrode (NT), IVA 3 mM, NT and RYA 3 mM. Cycle length (CL, ms) and diastolic depolarization rate (DDR, V/s) were also calculated. Both blockers displayed similar effects, increasing CL (by 27 and 30%, respectively), and decreasing DDR (by 34 and 42%) with respect to NT exposure. These results suggest that both mechanisms are involved into pacemaking mechanism at a similar degree.

scholarly journals Involvement of the persistent Na+ current in the diastolic depolarization and automaticity of the guinea pig pulmonary vein myocardium

2019 ◽  
Vol 141 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Masahiko Irie ◽  
Haruhito Hiiro ◽  
Shogo Hamaguchi ◽  
Iyuki Namekata ◽  
Hikaru Tanaka
Keyword(s):  
Guinea Pig ◽  
Pulmonary Vein ◽  
Na Current ◽  
Diastolic Depolarization

Normal spontaneous firing of cardiac pacemaker cells is regulated by basal pkc delta activation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Vinogradova ◽  
K Tarasov ◽  
D Riordon ◽  
Y Tarasova ◽  
E Lakatta
Keyword(s):  
Protein Kinase ◽  
Cycle Length ◽  
Cardiac Pacemaker ◽  
Funding Source ◽  
Spontaneous Firing ◽  
Pacemaker Cells ◽  
Patch Clamp Technique ◽  
Sa Node ◽  
Pkc Delta ◽  
Pkc Isoforms

Abstract   The spontaneous beating rate of rabbit sinoatrial node cells (SANC) is regulated by local subsarcolemmal calcium releases (LCRs) from sarcoplasmic reticulum (SR). LCRs appear during diastolic depolarization (DD) and activate an inward sodium/calcium exchange current which increases DD rate and thus accelerates spontaneous SANC firing. High basal level of protein kinase A and calcium/calmodulin-dependent protein kinase II phosphorylation are required to sustain basal LCRs and normal spontaneous SANC firing. Recently we discovered that basal PKC activation is also obligatory for cardiac pacemaker function: inhibition of PKC activity by broad spectrum PKC inhibitors Bis I or calphostin C markedly suppressed SR calcium cycling and decreased or abolished spontaneous beating of freshly isolated rabbit SANC. Here we studied which PKC isoforms mediate PKC-dependent effects on cardiac pacemaker cell automaticity. The PKC superfamily consists of 3 major subgroups: conventional, novel and atypical. All PKC isoforms were detected at the RNA level (RT-qPCR) in the rabbit SA node and ventricle, and expression levels were comparable in both tissues. Expression of PKCβ, however, was markedly higher in the rabbit SA node, compared to other PKC isoenzymes in either tissue. We verified expression of conventional PKC (α, β) and novel PKC-delta at the protein level in SANC and ventricular myocytes (VM). Western blot confirmed RNA results, showing a 6-fold higher PKCβ protein abundance in SANC compared to VM. Expression of PKCα protein was similar in both cell types, while PKC-delta protein was more abundant in VM. To study whether PKCβ regulates spontaneous beating of SANC we employed selective inhibitor of conventional (α, β, gamma) PKC isoforms Go6976 (10 μmol/L), which had no effects on either LCR characteristics (confocal microscopy, calcium indicator Fluo-3AM) or spontaneous beating of freshly isolated rabbit SANC (perforated patch-clamp technique). Because selective PKC-delta inhibitors are not available, we explored effects of PKC-delta inhibition comparing effects of Go6976 (the inhibitor of conventional PKCs) and Go6983, which inhibits conventional PKCs and PKC-delta. In contrast to Go6976, Go6983 (5 μmol/L) markedly decreased the LCR size (from 7.1±0.4 to 4.5±0.3 μm) and number per each spontaneous cycle (from 1.3±0.1 to 0.8±0.1). It also markedly increased the LCR period (time from the prior AP-induced calcium transient to the subsequent LCR) which was paralleled by an increase in the spontaneous SANC cycle length. Rottlerin, another PKC-delta inhibitor, produced similar effects on LCR characteristics, and markedly and time-dependently decreased DD rate, leading to an increase in the spontaneous cycle length, and finally abrogated the spontaneous SANC firing. Thus, our data indicate that basal activity of PKC-delta, but not that of PKCβ, is essential for generation of LCRs and normal spontaneous firing of cardiac pacemaker cells. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Intramural Research Program, National Institute on Aging, National Institute of Health, USA

Electroporation-Induced Inward Current in Voltage-Clamped Guinea Pig Ventricular Myocytes

2010 ◽  
Vol 238 (1-3) ◽  
pp. 69-80 ◽  
Author(s):  
Oksana Dyachok ◽  
Pavel Zhabyeyev ◽  
Terence F. McDonald
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Inward Current

Effects of Intravenous Anesthetics on Atrial Wavelength and Atrioventricular Nodal Conduction in Guinea Pig Heart

1996 ◽  
Vol 85 (2) ◽  
pp. 393-402 ◽  
Author(s):  
Charles A. Napolitano ◽  
Pekka M. J. Raatikainen ◽  
Jeffrey R. Martens ◽  
Donn M. Dennis
Keyword(s):  
Guinea Pig ◽  
Conduction Velocity ◽  
Cycle Length ◽  
Rank Order ◽  
Interelectrode Distance ◽  
Atrial Pacing ◽  
Dependent Manner ◽  
Frequency Dependent ◽  
His Bundle ◽  
Atrioventricular Nodal Conduction

Background Supraventricular tachydysrhythmias such as atrial fibrillation frequently complicate the perioperative period. Two electrophysiologic factors critical to the pathogenesis of supraventricular tachydysrhythmias are: 1) atrial wavelength, the product of atrial conduction velocity (CV) and effective refractory period (ERP), and 2) atrioventricular nodal conduction. Modulation of these factors by drugs has important clinical ramifications. The authors studied the effects of propofol, thiopental, and ketamine on atrial wavelength and atrioventricular nodal function in guinea pig isolated atrial trabeculae and hearts, respectively. Methods Electrocardiogram recordings in superfused atrial tissue were obtained using hanging microelectrodes. A stimulating and two recording electrodes were placed on a single atrial trabecula, and the interelectrode distance was measured. Atrial ERP determinations were made using a premature stimulus protocol. The time (t) required for a propagated impulse to traverse the interelectrode distance (d) was measured. Conduction velocity was calculated as d/t. Langendorff-perfused guinea pig hearts were instrumented for low atrial pacing (cycle length = 300 ms) and for measurements of stimulusto-His bundle interval, an index of atrioventricular nodal conduction. To investigate the frequency-dependent behavior of the atrioventricular node, computer-based measurements were made of Wenckebach cycle length (WCL) and atrioventricular nodal ERP. Results Thiopental significantly prolonged atrial ERP in a concentration-dependent manner, whereas propofol and ketamine had no significant effect on atrial refractoriness. In contrast, ketamine caused a dose-dependent decrease in atrial CV, but propofol and thiopental had no significant effect on CV. Therefore, thiopental, ketamine, and propofol caused an increase, a decrease, and no change, respectively, in atrial wavelength. All anesthetics caused a concentration-dependent prolongation of the stimulus-to-His bundle interval, atrioventricular nodal ERP, and WCL. However, on an equimolar basis, significant differences in potencies were found. The concentrations of drug that caused a 20% increase in ERP (ERP20) and WCL (WCL20) for propofol, thiopental, and ketamine were 14 +/- 2 microM, 26 +/- 3 microM, and 62 +/- 11 microM, and 17 +/- 2 microM, 50 +/- 1 microM, and 123 +/- 19 microM (mean +/- SEM), respectively. Therefore, the rank order of potency for frequency-dependent atrioventricular nodal effects is propofol > thiopental > ketamine. Conclusion The authors' results indicate that propofol would be most effective at filtering atrial impulses during supraventricular tachydysrhythmias, whereas thiopental would be most effective at preventing atrial reentrant dysrhythmias. In contrast, ketamine may be most likely to promote atrial reentry while having minimal effect on atrioventricular nodal conduction.

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