Mechanisms of Suppression and Initiation of Pacemaker Activity in Guinea-pig Sino-Atrial Node Superfused in High [K+]o

Kim, E.M.; Choy, Youyin; Vassalle, Mario

doi:10.1006/jmcc.1997.0382

Cited by 24 publications

(56 citation statements)

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“…In this connection, a major finding is that in the SAN perfused in suitably high [K + ] o the depolarization changes the subsidiary fast APs into slow responses [16][17][18][19][20]36]. This on the one hand decreases the Na + load due to the inactivation of the fast Na + channel (slow responses instead of fast APs) and on the other enhances the Ca 2+ load by overdrive (more slow responses and decreased rate of Ca 2+ extrusion).…”

Section: Calcium Load and Dominant Dischargementioning

confidence: 99%

“…Thus, in Tyrode solution, the pause was less affected than force by longer or faster overdrives. [17][18][19][20].…”

Section: Effects Of Overdrives Of Different Duration and Rate In Tyromentioning

confidence: 99%

“…As for the mechanism by which Ca 2+ extrusion might be less efficient in high [K + ] o with respect to Tyrode solution, one major difference is that in high [K + ] o the diastolic potential is less negative than in Tyrode solution [17][18][19][20]. Since the driving force for Ca 2+ extrusion is the Na + electrochemical gradient [14], a reduction of such a gradient due to the less negative diastolic potential would be expected to reduce Ca 2+ extrusion in the unit of time.…”

Section: Overdrive Increased Calcium Load and Forcementioning

confidence: 99%

“…If the behavior of the slow responses in high [K + ] o reflects that of dominant pacemakers (see below), the findings provide substantial insights in the operation of the SAN dominant pacemakers. This has to do with the presence of oscillatory potentials in the SAN [17][18][19][20].…”

Section: Calcium Load and Dominant Dischargementioning

confidence: 99%

“…In fact, overdrive of the cat SAN subsidiary pacemaker region surgically separated from the dominant region is followed by a prolonged inhibition [8], as in Purkinje fibers (''overdrive suppression'', [10]). Conversely, when in high [K + ] o SAN action potentials acquire the characteristics of dominant responses [16][17][18][19][20], overdrive may enhance or induce spontaneous discharge [18,20] (''overdrive excitation'', [21]). …”

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying overdrive suppression and overdrive excitation in guinea pig sino-atrial node

Vassalle

2006

J Biomed Sci

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SummaryThe hypothesis that the pause that follows overdrive of the sino-atrial node (SAN) might be the net result of overdrive excitation and overdrive suppression was tested by studying rate and force patterns induced by overdrive in isolated guinea pig SAN superfused in vitro. In Tyrode solution, the pause is short and changes but little with longer or faster drives. increases the rate as well as it shortens the pause, whereas Ni 2+ decreases force as well as rate and lengthens the pause. Barium dissociates the effects on force and rate. Lidocaine and tetrodotoxin decrease rate and force, and increase the pause duration. In overdrive excitation, the increase in rate is associated with an enhancement of diastolic voltage oscillations. It is concluded that in SAN the prevalence of Ca 2+ load leads to overdrive excitation whereas the prevalence of Na + load leads to overdrive suppression. In Tyrode solution, the pause after drive appears to be the net result of these two different mechanisms.Abbreviations: AP -action potential; MDP -maximum diastolic potential; DD -diastolic depolarization; R -control rate (prior to drive); F -control contractile force; DF 1 -force of first driven beat; DF 2 -force of last driven beat; pause -time interval between the last driven beat and the first spontaneous beat; PDF 1 -force of the first beat after the pause; PDR 1 -rate immediately after the pause; PDR 2 -late (10-15 s) postdrive rate; PDF 2 -late (10-15 s) post-drive force (see Figure 1); SR -sarcoplasmic reticulum; g K -K + conductance; a i Na -intracellular Na + activity; TTX -tetrodotoxin; NCX -Na + -Ca 2+ exchange current

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Section: Calcium Load and Dominant Dischargementioning

confidence: 99%

“…Thus, in Tyrode solution, the pause was less affected than force by longer or faster overdrives. [17][18][19][20].…”

Section: Effects Of Overdrives Of Different Duration and Rate In Tyromentioning

confidence: 99%

Section: Overdrive Increased Calcium Load and Forcementioning

confidence: 99%

Section: Calcium Load and Dominant Dischargementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying overdrive suppression and overdrive excitation in guinea pig sino-atrial node

Vassalle

2006

J Biomed Sci

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Differences in ionic currents between canine myocardial and Purkinje cells

Vassalle

Bocchi

2013

Physiol Rep

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An electrophysiological analysis of canine single ventricular myocardial (VM) and Purkinje (P) cells was carried out by means of whole cell voltage clamp method. The following results in VM versus P cells were obtained. INa3 was present, had a threshold negative to the fast activating-inactivating INa1, its slow inactivation was cut off by INa1, and contributed to Na+ influx at INa1 threshold. INa1 was smaller and had a less negative threshold. There was no comparable slowly inactivating INa2, accounting for the shorter action potential. Slope conductance at resting potential was about double and decreased to a minimum value at the larger and less negative IK1 peak. The negative slope region of I-V relation was smaller during fast ramps and larger during slow ramps than in P cells, occurred in the voltage range of IK1 block by Mg2+, was not affected by a lower Vh and TTX and was eliminated by Ba2+, in contrast to P cells. ICa was larger, peaked at positive potentials and was eliminated by Ni2+. Ito was much smaller, began at more positive values, was abolished by less negative Vh and by 4-aminopyridine, included a sustained current that 4-aminopyridine decreased but did not eliminate. Steeper ramps increased IK1 peak as well as the fall in outward current during repolarization, consistent with a time-dependent block and unblock of IK1 by polyamines. During repolarization, the positive slope region was consistently present and was similar in amplitude to IK1 peak, whereas it was small or altogether missing in P cells. The total outward current at positive potentials comprised a larger IK1 component whereas it included a larger Ito and sustained current in P cells. These and other results provide a better understanding of the mechanisms underlying the action potential of VM and P cells under normal and some abnormal (arrhythmias) conditions.

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Overdrive excitation in the guinea pig sinoatrial node superfused in high [K+]o

1997

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The aim of the present experiments was to study the characteristics and mechanisms of the rhythm induced by overdrive ('overdrive excitation', ODE) in the sinoatrial node (SAN) superfused in high [K(+)](o) (8-14 mM). It was found that: (1) overdrive may induce excitation in quiescent SAN and during a slow drive; (2) in spontaneously active SAN, overdrive may accelerate the spontaneous discharge; (3) immediately after the end of overdrive, a pause generally precedes the onset of the induced rhythm; (4) during the pause, an oscillatory potential (V(os)) may be superimposed on the early diastolic depolarization (DD); (5) during the subsequent late DD, a different kind of oscillatory potential appears near the threshold for the upstroke (ThV(os)) which is responsible for the initiation of spontaneous activity; (6) once started, the induced rhythm is fastest soon after overdrive; (7) faster drives induce longer and faster spontaneous rhythms; (8) the induced action potentials are slow responses followed by DD with a superimposed V(os), but ThV(os) is responsible for ODE; (9) the induced rhythm subsides when ThV(os) miss the threshold and gradually decay; (10) low [Ca(2+)](o) abolishes ODE; (11) in quiescent SAN, high [Ca(2+)](o) induces spontaneous discharge through ThV(os) and increases its rate by enhancing V(os) and shifting the threshold to more negative values, and (12) tetrodotoxin abolishes ODE as welll as the spontaneous discharge induced by high [Ca(2+)](o). In conclusion, in K(+)-depolarized SAN, ODE may be present in the apparent absence of calcium overload, is Ca(2+)- and Na(+)-dependent and is mediated by ThV(os) and not by V(os). Copyright 1997 S. Karger AG, Basel

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Mechanisms of Suppression and Initiation of Pacemaker Activity in Guinea-pig Sino-Atrial Node Superfused in High [K+]o

Cited by 24 publications

References 0 publications

Mechanisms underlying overdrive suppression and overdrive excitation in guinea pig sino-atrial node

Mechanisms underlying overdrive suppression and overdrive excitation in guinea pig sino-atrial node

Differences in ionic currents between canine myocardial and Purkinje cells

Overdrive excitation in the guinea pig sinoatrial node superfused in high [K+]o

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