Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H122-H132
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Channel Blockers ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Current Voltage ◽  
Current Voltage Relation

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.

Cycle length-dependent action potential duration in canine cardiac Purkinje fibers

1984 ◽  
Vol 247 (6) ◽  
pp. H936-H945 ◽  
Author(s):  
V. Elharrar ◽  
H. Atarashi ◽  
B. Surawicz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cycle Length ◽  
Slow Inward Current ◽  
Tetraethylammonium Chloride ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Kinetics Of

We studied the effects of pharmacologic probes that affect predominantly the Na inward current [tetrodotoxin (TTX), lidocaine], the slow inward current [cobalt, isoproterenol, verapamil], and the potassium currents [tetraethylammonium chloride (TEA), SG-75] on the duration of the action potential (APD) of canine cardiac Purkinje fibers during steady state and restitution. A schema is proposed in which the APD during steady state or restitution is determined by three factors: maximum action potential duration (APDmax), kinetics of restitution, and “memory.” The predicted APDmax was 469 +/- 34 (SE) ms (n = 27) in control. It was prolonged (P less than 0.05) by cobalt, verapamil, and TEA and shortened (P less than 0.05) by TTX, lidocaine, isoproterenol, and SG-75. In control, the kinetics of restitution were described by a sum of two exponentials with time constant T1 = 137 +/- 9 ms and T2 = 1,665 +/- 135 ms (n = 27), respectively. T1 was prolonged (P less than 0.05) by TTX, lidocaine, and verapamil but was not changed by other probes. None of the probes studied altered the T2 of restitution or the memory factor, computed at a cycle length of 500 ms from the predicted APDmax and the plateau of restitution. Low temperature (31 degrees C) prolonged APDmax and T1 and reduced the memory. We conclude that each of the proposed three factors is controlled by different mechanisms and that a TTX-sensitive current appears to contribute to the process of restitution of APD.

scholarly journals 4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers.

1979 ◽  
Vol 73 (2) ◽  
pp. 139-157 ◽  
Author(s):  
J L Kenyon ◽  
W R Gibbons
Keyword(s):  
Action Potential ◽  
Phase 1 ◽  
Outward Current ◽  
Blocking Agent ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Background Current ◽  
Cardiac Purkinje Fibers ◽  
Steady State Current ◽  
Early Peak

We have studied the effects of the potassium-blocking agent 4-aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In the presence of 4-AP, the substitution of sodium methylsulfate or methanesulfonate for the NaCl of Tyrode's solution further slowed the rate of phase 1 repolarization, even though chloride replacement has no effect on the untreated preparation. In voltage clamp experiments, 4-AP rapidly and reversibly reduced the early peak of outward current that is seen when the Purkinje fiber membrane is voltage-clamped to potentials positive to -20 mV. In addition, 4-AP reduced the steady outward current seen at the end of clamp steps positive to -40 mV. 4-AP did not appear to change the slow inward current observed over the range of -60 to -40 mV, nor did it greatly change the current tails that have been used as a measure of the slow inward conductance at more positive potentials. 4-AP did not block the inward rectifying potassium currents, IK1 and IK2. A phasic outward current component that was insensitive to 4-AP was reduced by chloride replacement. We conclude that the early outward current has two components: a chloride-sensitive component plus a 4-AP-sensitive component. Since a portion of the steady-state current was sensitive to 4-AP, the early outward current either does not fully inactivate or 4-AP blocks a component of time-independent background current.

A re-examination of late outward plateau currents of cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H108-H121
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Critical Role ◽  
Membrane Current ◽  
Purkinje Fiber ◽  
Purkinje Fibers ◽  
Outward Currents ◽  
Cardiac Purkinje Fibers

Two outward currents, IX1 and IX2, are thought to be activated by depolarization of the Purkinje fiber. One of these, IX1, is presently believed to play a critical role in repolarization of the action potential. The IX currents were originally analyzed in voltage-clamp experiments in sheep Purkinje fibers. These experiments were designed to minimize interference by other currents, and it was assumed that changes of the net current were produced entirely by the IX currents. We have tried to repeat the original experiments and the analysis that led to acceptance of the existence and roles of the IX currents, without success. Moreover, tests of how membrane current should behave if the IX current hypothesis is correct did not give satisfactory results. Our data suggest the original conclusions about IX1 and IX2 may need substantial revision.

Participation of slow inward current in the Purkinje fiber action potential overshoot

1979 ◽  
Vol 237 (2) ◽  
pp. H204-H212
Author(s):  
L. Mary-Rabine ◽  
B. F. Hoffman ◽  
M. R. Rosen
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Inward Current ◽  
Slow Channel ◽  
Phase 0 ◽  
Relationship Of ◽  
The Relationship ◽  
Diastolic Potential

We used microelectrode techniques to study the relationship of canine Purkinje fiber membrane potential and the action potential (AP) overshoot. At the maximum diastolic potential, -93.0 +/- 0.5 (SE) mV, AP overshoot was +37.7 +/- 0.4 mV. There was a range of membrane potentials (MP) less negative than the maximum diastolic potential from which action potentials were elicited with an overshoot greater than the control. Starting at an MP of less than -78.7 +/- 0.4 mV, AP overshoot was less than control. A maximum overshoot of +40.2 +/- 0.4 mV occurred at an MP of -85.4 +/- 0.4 mV. The relationship of the maximum upstroke velocity (Vmax) of phase 0 depolarization to MP was sigmoidal. Peak Vmax, 497 +/- 13 V/s, occurred at MP greater than or equal to -89.3 +/- 0.5 mV. The increase in overshoot was enhanced as perfusate [Ca2+] increased and decreased as [Ca2+] decreased. Slow-channel blocking agents and tetrodotoxin (TTX) depressed the peak of the curve relating overshoot to MP. TTX also decreased Vmax. The effect of TTX on overshoot but not on Vmax was reversed with Ca2+, 8.1 mM. The increase in overshoot for action potentials initiated during the terminal part of phase 3 was due to a slow, delayed component of the upstroke and appears to result from the slow inward current.

Caffeine-induced current in embryonic heart cells: time course and voltage dependence

1983 ◽  
Vol 245 (3) ◽  
pp. H528-H532 ◽  
Author(s):  
W. T. Clusin ◽  
R. Fischmeister ◽  
R. L. DeHaan
Keyword(s):  
Time Course ◽  
Reversal Potential ◽  
Myocardial Cell ◽  
Slow Inward Current ◽  
Heart Cells ◽  
Induced Current ◽  
Inward Current ◽  
Current Voltage ◽  
Micron Diameter ◽  
Current Voltage Relation

Abrupt exposure of 90- to 130-micron diameter chick embryonic myocardial cell aggregates to 10 mM caffeine has been shown to induce a transient inward current. In the present study, we recorded a similar current in small cell clusters (less than 10 cells) in which access of caffeine to each of the cells was rapid. The resulting inward current consisted of a single peak, which decayed exponentially (predominant time constant 335 +/- 130 ms at -40 mV) and had a peak amplitude of up to 15.5 microA/cm2. The caffeine-induced current persisted when the slow inward current was abolished by a 30-s pretreatment with 2 microM D 600 and could be observed at potentials where the fast sodium channels were fully inactivated. The current-voltage relation of the caffeine response was linear between -110 and -40 mV, giving an extrapolated voltage intercept of +12 mV. However, the inward current did not diminish or reverse with further depolarization. A substantial inward current occurred at potentials up to +60 mV, which is more positive than the reversal potential of the tetrodotoxin-sensitive inward current. We conclude that the caffeine-induced current is mediated in part by electrogenic Na+-Ca2+ exchange.

Voltage-dependent Ca2+ channel and Na+ channel in frog taste cells

1983 ◽  
Vol 244 (1) ◽  
pp. C82-C88 ◽  
Author(s):  
M. Kashiwayanagi ◽  
M. Miyake ◽  
K. Kurihara
Keyword(s):  
Current Pulse ◽  
Lingual Artery ◽  
Na Channel ◽  
Channel Blockers ◽  
Inward Current ◽  
Current Voltage ◽  
Taste Cells ◽  
Voltage Dependent ◽  
Current Voltage Relation ◽  
Ca2 Channels

Frog taste cells were hyperpolarized by injecting an inward current pulse, and regenerative anode-break potentials were observed at the termination of the current pulse. The results obtained are as follows. 1) The magnitude of the anode-break potentials increased with the extent of hyperpolarization of taste cells and reached a saturation level around -200 mV. 2) The magnitudes of the anode-break potentials observed in 80 different taste cells hyperpolarized to about -200 mV were distributed widely from cell to cell. The average magnitude was 39 mV. 3) The anode-break potentials were recorded after the lingual artery was perfused with artificial solutions containing various channel blockers. The results indicated that the anode-break potentials are composed of Na+ and Ca2+ components. 4) The slope of the current-voltage relation obtained with cells hyperpolarized to 100 mV was appreciably decreased above -50 mV by application of tetrodotoxin to the perfusing solution. Discussion was made on possible roles of the voltage-dependent Na+ and Ca2+ channels in the electrotonic spreading of the depolarization at the receptor membranes to the synaptic area and in releasing a chemical transmitter.

Effects of 4-aminopyridine on rate-related depression of cardiac action potentials

1986 ◽  
Vol 251 (2) ◽  
pp. H297-H306 ◽  
Author(s):  
R. F. Gilmour ◽  
J. J. Salata ◽  
J. R. Davis
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Membrane Potentials ◽  
Action Potential Amplitude ◽  
Bundle Branch Block ◽  
Purkinje Fibers ◽  
Potential Amplitude ◽  
Cardiac Purkinje Fibers ◽  
Sucrose Gap

Canine cardiac Purkinje fibers and atrial trabeculae and rat and cat papillary muscles superfused with a hyperkalemic, hypoxic, and acidotic Tyrode solution were depolarized to membrane potentials (-70 to -60 mV) at which action potential amplitude declined as the coupling intervals of pacing stimuli were prolonged from 500 to 4,500 ms. The rate-related decline of action potential amplitude appeared to be due to time-dependent recovery of the early outward current rather than to a decrease in inward calcium current, since it was prevented by 4-aminopyridine (1.0 mM), but not by isoproterenol (1.0 microM), caffeine (5.0 mM), or CsCl (5-20 mM) and it was accompanied by an exponential increase of developed tension. Experiments using Purkinje fibers mounted in a single sucrose gap chamber demonstrated that the rate-related decline of action potential amplitude was maximal at membrane potentials between -70 and -40 mV and was negligible at less negative or more negative membrane potentials. These results may pertain to the mechanism for deceleration-dependent bundle branch block.

scholarly journals Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers.

1975 ◽  
Vol 66 (2) ◽  
pp. 169-192 ◽  
Author(s):  
R S Kass ◽  
R W Tsien
Keyword(s):  
Action Potentials ◽  
Membrane Surface ◽  
Outward Current ◽  
Inhibitory Influence ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Ca Antagonist ◽  
Ca Ions ◽  
Membrane Surface Charge

We studied the influence of Mn, La, and D600 on action potentials and plateau currents in cardiac Purkinje fibers. The Ca antagonists each abolished the second inward current, but they failed to act selectively. Voltage clamp experiments revealed two additional effects: decrease of slow outward current (iotachi) activation, and increase of net outward time-independent plateau current. These effects occurred at inhibitor concentrations used in earlier studies, and were essential to the reconstruction of observed Ca antagonist effects on electrical activity. The inhibitory influence of Mn, La, and D600 on iotachi suggested that iotachi activation might depend upon prior Ca entry. This hypothesis was not supported, however, when [Ca]omicron was varied: elevating [Ca]omicron enhanced Ca entry, but iotachi was nevertheless depressed. Thus, the results suggested instead that Ca antagonists and Ca ions have rather similar effects on iotachi, possibly mediated by changes in membrane surface charge.

scholarly journals Slow inward current and contraction of sheep cardiac Purkinje fibers.

1975 ◽  
Vol 65 (3) ◽  
pp. 367-384 ◽  
Author(s):  
W R Gibbons ◽  
H A Fozzard
Keyword(s):  
Intracellular Calcium ◽  
Voltage Clamp ◽  
Mammalian Species ◽  
Slow Inward Current ◽  
Ventricular Muscle ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Rate Of Recovery ◽  
Calcium Pool

A "slow" inward current (Is) has been identified in ventricular muscle and Purkinje fibers of several mammalian species. The two-microelectrode voltage clamp technique is used to examine some of the relationships between Is and contraction of the sheep cardiac Purkinje fiber. "Tails" of inward current occurring on repolarization and extrapolation of Is recovery each show that the Is system may not inactivate completely during prolonged depolarization. The rate of recovery of Is after a depolarization is slow, and when a train of 300-ms clamps (frequency 1 s-1) is begun after a rest, Is is larger for the first clamp than it is for succeedings clamps. For the first clamp after a rest, the thresholds for Is and tension are the same and there is a direct correlation between peak tension and peak Is for clamp voltages between threshold and minus 40 mV. After a clamp, however, the ability to contract recovers much more slowly than does Is. Therefore, since Is may occur under certain conditions without tension, the realtionship between Is and tension must be indirect. Calcium entering the cell via this current may replenish or augment an intracellular calcium pool.

Sign in / Sign up

Export Citation Format

Share Document