The electrophysiological analysis of ouabain sensitivity of mouse and guinea pig sinoauricular node cells
Authors: Lebedeva Elena , Pasatetskaya Natalya , Gonotkov Mikhail , Nuzhny Vladimir , Lopatina Ekaterina , Golovko Vladimir 
Published: June 2021

Introduction

It is known that Na+/K+‐ATPase isoforms differ significantly in their response to the cardiac glycosides. Thus, the organism reactions to glycoside are species‐dependent.

The aim of the present study was to assess the impact of the Na+/K+‐ATPase current on electrical activity of mice and guinea pigs sinoauricular (SA) node.

Methods

The experiments were conducted on male albino mice (age 8–10 weeks, body mass 30±5 g, n=14) and male guinea pigs (age 4–5 months, body mass 550±50 g, n=7). The action potentials (APs) were registered in the isolated SA region strips from the side of subendocardial side along the SA artery using standard microelectrode method.

Results

The cells with spontaneous APs generation and the slowest maximal upstroke velocity in phase 0 (dV/dtmax) – 3.2±0.7 and 4.1±2.7 V/s, in mouse and guinea pig respectively (Table 1.) – and with the diastolic depolarization (DD) phase (phase 4, diastole) were identified in control Tyrode's solution. The spontaneous APs generation frequencies at 31°C were 286±16 min−1 in mice myocardium strips and 103±30 min−1 in guinea pigs strips. The exposition of mice SA myocardium strips to ouabain (1 μmol/l, n=5) decreased the APs generation frequency by 10% as a result of the 17% increase of the AP duration at 90% repolarization (APD90) (Table 1.). These changes were accompanied by the 28% decrease of dV/dtmax. The exposition of guinea pig SA node cells to ouabain (1 μmol/l, n=4) decreased the DD phase duration by 30% and therefore increased the APs generation frequency by 23% (Table 1.) The higher concentrations of ouabain (10 μmol/l instead of 1 μmol/l) decreased the APs generation frequency in the mouse SA cells (n=9) by 14% due to the 20–25% increase of both APD90 и DD. The diastolic depolarization rate (V4) и dV/dtmax decreased by one third (Table 1.). The higher concentrations of ouabain (10 μmol/l) blocked the electrical activity in guinea pig SA strips (n=3) after 11±2 min of compound treatment. At the same time, the sarcolemma depolarization, decreased AP amplitude and dV/dtmax as well increased APs generation frequency by 35% (on average) due to shorter DD phase were registered (Figure 1). In mouse SA strips (n=3) ouabain in concentration 100 μmol/l at first decreased APs generation frequency by 24%, and then totally suppressed the electrical activity in the cells.

We assumed that the observed effects of ouabain were not only a result of different sensitivity of Na+/K+‐ATPase isoforms, but also of higher intracellular concentration of ([Na+]i) in mice compared to guinea pigs. Our findings suggest that differences in pacemaker activity mechanisms in these two species should be taken into account when testing the prospective pharmacological compounds for treatment of dysrhythmias of different origin and developing mathematical models of APs generation.

Support or Funding Information

The study was supported by project № AAAA‐A17‐117012310152‐2 and № AAAA‐A18‐ 118012290365‐2

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.