The Contribution Na‐Current in Generation of tje Upstroke of Action Potential in the Cells of Sinoauricular Region of Mouse, Guinea Pig, Rabbit and Pig
Authors: Lebedeva Elena , Golovko Vladimir 
Published: November 2023

Background

The role of the Na+‐current in generation of upstroke in the cells with the slower dV/dtmax remains controversial. The data obtained on different mammalian species is needed to understand the exact physiological mechanisms underlying pacemaker activity in the sinoauricular (SA) node.

The aim of the present study was to verify the hypothesis about the contribution of the inward Na‐current sensitive to lidocaine in generation of the upstroke phase of action potentials (AP) in sinoauricular node cells with the slowest dV/dtmax (3–7 V/s) in mouse, guinea pig, rabbit and pig.

Methods

The experiments were performed on albino male mice (30–35 g, 2 months of age), male guinea pigs (500–600 g, 4–5 months of age), male rabbits (3–3.5 kg, 6–7 months of age) and male pigs (45–50 kg, 4–5 months of age). The intracellular APs were recorded from sinoauricular strips using microelectrode technique.

Results

The action potentials of cells with slow diastolic depolarization (DD) were recorded from the side of subendocardium in the region of sinoauricular node artery. In mouse (n=6) the dV/dtmax and the AP generation rate were 2.6±0.7 V/s and 295±28 beats per min (M±σ). In guinea pig (n=5) the dV/dtmax and the AP generation rate were 2.7±1 V/s and 107±19 bpm. In rabbit (n=5) the dV/dtmax and the AP generation rate were 6.9±1,3 V/s and 107±14 bpm. In pig (n=5) the dV/dtmax and the AP generation rate were 2.2±0,5 V/s and 48±8 bpm.

In true pacemaker cells of mouse's SA node the treatment with lidocaine (50 μM) increased the duration of the peak APD20 by 50%, slowed the dV/dtmax by 62% (from 2.6±0.8 to 1±0.2 V/s, p≤0.05) and reduced the velocity of DD (V4) by 20% in comparison with control. As a result, the spontaneous rate of AP generation was decreased by 23% (Fig. 1A).

In pacemaker cells of guinea pig lidocaine in concentration 50 μM decreased the amplitude of AP by 26% and slowed the dV/dtmax by 52% (from 2.7±0.8 to 1.3±0.5 V/s, p≤0.05). The DD velocity slowed by 45%. Thus, the rate of generation of AP was reduced by 25% in comparison with control (Fig. 1B).

However, lidocaine in this concentration had no effect on generation of action potentials in pacemaker cells of rabbit. The increase of lidocaine's concentration from 50 to 500 μM caused a decrease in the amplitude of AP by 14% and decreased the dV/dtmax by 57% (from 6.9±1.3 to 3.0±1.7 V/s, p≤0.05). The duration of the peak of AP (phase 2, APD20) was lengthen by 30%, DD velocity was slowed by 21%. As a result, the spontaneous rate of AP generation was decreased by 15% (Fig. 1C).

In pig's SA node cells lidocaine (50 μM) slowed the dV/dtmax by 52% (from 2.2±0.5 to 143±0.1 V/s, p≤0.05) and the DD velocity – by 33%. Furthermore, the spontaneous rate of AP generation was decreased by 23% in comparison with control (Fig. 1D).

Conclusions

The data indicate that the AP dV/dtmax of studied cells was reduced by 35–60% after addition of the specific inward Na‐current blocker lidocaine in all studied mammalian species. The contribution of Na+‐currents in rate of AP generation is about 23–25% in mice, guinea pigs, pigs, and about 15% in the rabbit. Furthermore, the pacemaker cells of rabbit's SA node were about 10 times more resistant to inhibition of Na+ ‐channels with lidocaine compared to other studied species. The participation of lidocaine‐sensitive‐current simultaneously with the Ca2+‐current of L‐type increases the reliability of the generation of action potentials in true pacemaker cells in the sinoauricular node center.

Support or Funding Information

Supported by the Ural's Division RAS projects 15‐5‐4‐11