Characterization of changes in the configuration of action potentials in the mouse, guinea pig, and pig sinoauricular node after application of channel blockers of the rapid and slow delayed rectifier potassium currents.

We hypothesized that the repolarization phase of action potentials (APs) in mammals with large body mass and high cardiac output could not be reliably controlled by only one of the delayed rectifier potassium IK current components. To test this hypothesis experimentally, we performed a comparative study of the response of AP phases to the rapid IKr channels blocker E-4031 and slow IKs blocker chromanol 293B in APs spontaneously generated in strips of sinoauricular (SA) tissue from mouse, guinea pig, and pig hearts. Application of a slow channels blocker chromanol 293B caused a decrease of Aps generation frequency in SA area strips from mouse, guinea-pig and pig by 5.3, 16, and 18% compared to the control. Treatment with the IKr blocker E-4031 caused a significant reduction of APs generation frequency in the mouse, guinea pig, and pig SA strips by 24, 26, and 36%, respectively, compared to the control values. These results suggest that the rapid IKr current is the key component responsible for AP generation in sinoauricular node cells of the pig heart.

Aminopyridine lengthened the plateau phase of action potentials in mouse sinoatrial node cells.

Duration of the plateau phase (phase 2) of action potentials in pacemaker cells in mouse sinoatrial node characterized by low upstroke rate during the rapid depolarization (dV/dt max <7 V/sec, phase 0) and in atrial-like cells with dV/dt max <100 V/sec were prolonged by 50% with 4-aminopyridine in concentrations of 0.7 and 0.1 mM, respectively. This blocker did not lengthen the terminal repolarization (phase 3). The above changes were accompanied by a 20-80% decrease in dV/dt max in comparison to the control. It is hypothesized that the short-term (transient) outward current Ito takes a part in the plateau formation and modulates the duration of the rapid depolarization phase of action potentials in mouse sinoatrial node cells.

[The involvement of lidocaine and tetrodotoxin-sensitive current in the generation of action potentials with low DV/DT max in the cells of the mouse sinoauricular region].

The effects of the specific blockers of the inward Na-current --lidocaine and tetrodotoxin (TTX) were studied with microelectrode technique on the spontaneously beating strips of the mouse sinoauricular (SA) area. Lidocaine (25 microM) and TTX (25 pM) increased the duration of the peak of the action potentials (AP) of true pacemaker cells by extending the plateau phase (phase 2 or APD 20), slowing the dV/dt max from 2.6 +/- 0.8 V/s (n = 25) to 1.4 +/- 0.3 V/s (n = 5, p < 0.05) and reducing the velocity of diastolic depolarization (DD) by 20%. The extend of the dV/dt max value decline depended on the lidocaine concentration. The experimental data fully meted to Hill equation. The lidocaine threshold concentration was 20 microM. The lidocaine effective concentration which decreased dV/dt max by 50% (EC50) was 35 microM. The TTX (25 microM) exposure decreased the dV/dt max from 1.6 V/s to 0.8 V/s and DD velocity slowed by 49%. It should be noted that TTX also increased the duration of APD20. Our data show that dV/ dt max of the true pacemaker cells was reduced by 35-45% after exposure to TTX and lidocaine. This fact confirms the involvement of Na-current in the generation of the upstroke true pacemaker cells AP.

[Mechanism of outercellular [K+] in generation of pacemaker action potentials in sinoatrial valve of the rabbit].

In a control solution (solution I; 3 mM K+, 35 degrees C) the amplitude of APs of cells in the valve centre was 81 +/- 6 mV (Mean +/- SEM), the maximal upstroke velocity (dV/dtmax) was 19 +/- 4 V/s, velocity slow diastolic depolarization (DD) - 65 +/- 8 mV/s, the rate of spontaneous AP generation was 135 +/- 14 bpm. Hypo K+ (50 %) solution (solution II) decreased slow DD by - 22 % and dV/dtmax by -58 % and the rate of AP generation by 15 % compared to the control solution. In saline solution, decrease of Emax from -68 to -45 mV and four-fold decrease of slow DD and dV/dtmax were registered at the 8th of exposure. After that the Emax noise and origin of early (EADs) and delay (DADs) afterdepolarizations were observed. Comparative analysis of the main AP parameters of SA valve latent pacemaker cells in solution III (without K+) and solution IV (without KC1 and CaCl2) exposure demonstrated that changes of this parameters in solution IV were less then in solution III. It is interesting that in solution IV exposure the phase of the early repolarization (phase 1) was differentiated, dV/dtmax was increased by 21%. The frequency of AP generation decreased by 18 % as in solution with 50% K+. At the same time, EADs were not registered. It seems that the decreasing of the transsarcolemal gradient of K+ depolarized Emax despite Nernst equation. At the same time permeability was decreased for K+ and Na+ ions. That could involve Ca2+ overload and origin of EADs and DADs.

The negative chronotropic effect of Cs(+) ions on generation of transmembrane potentials in mouse sinoatrial node cells.

Experiments on spontaneously contracting strips from sinoatrial region of the hearts of 2-month-old albino mice showed that cesium (Cs(+)), a blocker of hyperpolarization-activated I(f) current, in a concentration of 1 mM produced the greatest negative chronotropic effect on the duration of diastolic depolarization phase (75%), its rate (59%), and action potential duration (29%). The threshold concentration of Cs(+) was approximately 0.15 mM. In a concentration of about 8.5 mM, spontaneous generation of action potentials stopped. The effect was reversible. Thus, blockade of I(f) current by Cs(+) reduced the rate of action potential generation in cells of mouse sinoatrial node by app. 42% in comparison with controls.

[Slow activated voltage-dependent sodium current contribution in fast depolarization in the rabbit heart true pacemaker sinoatrial node].

The functional role of INa in initiation and conduction of cardiac true pacemaker activity remains uncertain. Therefore the goal of this work was to study the effects of Na+ substitution of action potentials parameters of the sinoatrial area cells. Transmembrane action potentials were recorded with 15 to 40 MOmega glass microelectrodes filled with 2.5 M KCl. The final preparations was about 5 x 3 mm in size, contained a portion sinoatrial node and the adjacent fragment of tissue of the right branch of the sinoatrial ring bundle and crista terminalis. All strips were allowed to beat spontaneously. We have registered that Na+ replacement of 50% in external solution causes an almost two-fold monotonous decrease of dV/dtmax and overshoot values of primary (3.2 V/s, n = 15), latent pacemaker (17 V/s, n = 16) and "conducting"-like cells (130 V/s, n = 16, control, 35 C) as compared with the control. Finally (at 30 min exposure) action potential frequency is slowed dowb by 20-30%. True pacemaker cells decreased action potential amplitude from 65 to 9 mV for 20-30 min 50% Na solution exposure. It should be noted that the cells of the "conducting"-like type demonstrated the generation block of action potential 30% Na exposure. At the same time dV/dtmax monotonously decreased from 3.1 to 1.5 V/s (true pacemaker) 16 vs 7 V/s (latent) and from 130 to 1.8 v/s ("conducting"). In our opinion, these facts deserve particular attention because it has been reported earlier that tetrodotoxin (20 mcM) addition in to the control solution caused the decrease of dV/dt from 100 to 4 V/s in latent pacemaker, whereas action potential amplitude is decreased by only some mV and the rate of beating by 1.5 times. As for true pacemaker cells, the TTX does not influence them.

Stabilizing effect of Silene pectin polysaccharide on electrical activity of the sinoatrial area in frog heart.

Silenan, a pectin polysaccharide from common catchfly (Silene vulgaris), corrects disorders in the conduction of action potentials between cells of the sinoatrial area of frog heart forming a functional syncytium. Recovery of action potential conduction in the sinoatrial cells was recorded in long-term experiments (>8 h). The effect of silenan manifested mainly against the background of arrhythmic generation and impaired propagation of action potentials.

Single and multiple early afterdepolarization caused by nickel in rat atrial muscle.

We examined the possible role of the Na-Ca exchange (NCX) in the arrhythmogenesis in rat atrial preparations applying microelectrode technique. In control Tyrode solution preparations isolated from the sinoatrial area contracted with frequency of 48+/-4 min(-1) (group I) or 84+/-7 min(-1) (group II). In preparation beating with low frequency partial inhibition of NCX by administration of Ni2+ (0.3 mmol/l) to the bath solution caused single early afterdepolarization (EAD) on the 15th min. During the following five minutes they were transformed into multiple EADs from 4 to 47 (action potentials) with general duration of 1-12 s. The effects were reversible. Ni2+ (0.3 mmol/l) in the preparations beating with higher rate (group II) did not cause multiple EADs, but after higher Ni2+ concentration (0.5 mmol/l) single EAD was observed more often. It was concluded that Ca2+ overload due to partial block of the NCX can contribute to the development of atrial tachyarrhythmias.

[Single "early" action potential cause by Ni2+ ions in true pacemaker cells of the sinoatrial ring of the dace heart]. / Odinochnye "rannie" potentsialy deistviia, vyzvannye ionami Ni2+, u istinno peismekernykh kletok sinusno-predserdnogo kol'tsa serdtsa el'tsa.

Single "early" action potentials (AP) or "early" postdepolarization (EAD) were recorded in multicellular stripes working in the regimen of true pacemaker cells located in the basis of the sinoatrial valve of the dace (Leuciscus rutilus) heart after Ni2+ (0.3 mM) were added to superfused solution on the 15 th min. The standard microelectrode technique was used. The appearance of single EAD was preceded by increase of AP spike duration almost 1.5-fold due to increase of the duration of a final repolarization phase and of diastolic depolarization. EADs appeared at different levels of repolarization from -20 to -60 mV. EAD's amplitude was lower than the AP proper. The effect is reversible. Nifedipine (2 microM) decreased by 20% the AP duration to 50% repolarization in the cells of atrial type. In case the stripes were primarily subjected to nifedipine effect and then even after a long procedure of washout, the Ni2+ (0.3 mM) did not cause EADs. The hypothesis has been tested of what is the main reason of single EAD appearance in pacemaker cells under the effect of Ni2+; it is either blocking Ca release from the cell by Ni2+, or reactivation of L-type Ca-channels' conductivity. The analysis of the data obtained leads to the conclusion that 30-50% Na-Ca-exchangers block is the basic reason of single EAD appearance in pacemaker cells.

[The dispensary observation of patients with chronic nonspecific lung diseases who work in a dust-producing industry with a high radionuclide level as a consequence of the accident at the Chernobyl Atomic Electric Power Station]. / Dispansernoe nabliudenie za bol'nymi khronicheskimi nespetsificheskimi zabolevaniiami legkikh, rabotaiushchimi na pylevom proizvodstve s povyshennym soderzhaniem radionuklidov vsledstvie avarii na Chernobyl'skoi AES.

Patients working at a small mining institution and suffering of chronic unspecific pulmonary diseases due to high dust and radionuclide contamination levels were examined. Four groups of dispensarization were singled out with the purpose of differential treatment for each group. Such treatment including also antiaggregant agents, nitro-drugs resulted in a good medico-social effect within 2 years.

[Iridodiagnosis in the system of the follow-up of the health status of the population living in an area contaminated by radioactive substances]. / Iridodiagnostika v sisteme kontrolia za sostoianiem zdorov'ia naseleniia, prozhivaiushchego na territorii, zagriaznennoi radioaktivnymi veshchestvami.

The authors substantiate the practical employment of the iridodiagnosis screening-test using a system of archiving and visualization of the iris at the first stage of prophylactic medical examination and management. The economical and medical efficacy of the method has been established. Use of iridodiagnosis improved the detectability of pathologic conditions as compared with complex medical examination. Many specialists were freed from mass medical screening. The expenses for prophylactic medical examination became ten times less.

Modelling of the effects of Na+ and Ca2+ ions on the generation of action potentials by rabbit heart true pacemaker cells.

A comparison of results of modelling and physiological experiments allowed to estimate in the first approximation the quantitative contribution of calcium and sodium ions to the generation of different ionic currents determining the shape of the action potential (AP). Generally, the model reproduced adequately variations in AP shape with changes in the external concentrations of Na+ and Ca2+. At the same time the model differs slightly from the experimental results. To improve the model kinetic variables of slow inward current have to be taken into account.

[Effects of sodium and calcium ions on the potentials of cardiac pacemaker cells in the frog]. / Effekty ionov natriia i kal'tsiia na potentsialy kletok voditelia ritma serdtsa liagushki.

True and latent pacemaker cells were differentiated in the frog heart sino-atrial area. Within the first 5 min in the hyposodium solution, a decrease of the overshoot and maximal velocity of depolarization occurred. The true pacemaker cells did not reveal any changes of the AP parameters within 30-60 min. The cells of true pacemaker exhibited a higher sensitivity to the hypocalcium solution. The data obtained suggested a scheme of the whole cycle of Na+, K+ and Ca2+ exchange.