Existence of two transient outward currents in sheep cardiac Purkinje fibers

Coraboeuf, E; Carmeliet, Edward; Prenen, Jean

doi:10.1007/bf00581631

Cited by 212 publications

(145 citation statements)

References 35 publications

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“…Nevertheless, it remains possible that an additional factor contributing to the effect on the early phase is a reduction of a transient outward current by strontium. Such an inhibitory effect of strontium on outward currents has been seen in Purkinje fibres (Siegelbaum & Tsien, 1980;Coraboeuf & Carmeliet, 1982). The contribution of an outward current to early repolarization in calcium-containing solution is shown by the effect of 4-AP, which prolongs the early phase of the action potential.…”

Section: Discussionmentioning

confidence: 89%

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Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle

Mitchell

Powell

Terrar

et al. 1984

British J Pharmacology

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Action potentials, initiated by brief depolarizing pulses, were recorded from single cells isolated from rat ventricular muscle. These action potentials showed a rapid upstroke to about + 30 mV, followed by two phases of repolarization referred to as the early and late phases of the action potential. Nifedipine (1 μm), which blocks the second inward current (Isi) carried by Ca in these cells, shortened the early phase. Substitution of strontium for calcium in the solution bathing the cells, a procedure which prolongs Isi, prolonged the early phase. 4‐Aminopyridine (1 mm), which inhibits transient outward current, prolonged the early phase with either calcium or strontium in the external solution. It is concluded that both Isi and transient outward current contribute to the early phase of the action potential in rat ventricular muscle. It is also suggested that Isi does not directly contribute to the late phase, since the characteristics of the late phase are not compatible with such a role, and the possibility of additional inward current is investigated in the accompanying paper (Mitchell et al., 1984).

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Section: Discussionmentioning

confidence: 89%

“…Prolongation of the early phase by 4-AP also occurred when strontium was substituted for calcium ( Figure 5b). 0-a i (Siegelbaum & Tsien, 1980;Coraboeuf & Carmeliet, 1982), the prolongation by 4-AP suggests that substantial outward current remains in the presence of strontium.…”

Section: Action Potential Time Course and 4-aminopyridinementioning

confidence: 99%

Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle

Mitchell

Powell

Terrar

et al. 1984

British J Pharmacology

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“…Two types of transient K+ currents have been reported in cardiac muscle cells (Coraboeuf & Carmeliet, 1982;Escande et al, 1987). These possibilities could be distinguished by use of single channel recordings.…”

Section: Effects Of Cpz On Itmentioning

confidence: 99%

“…(1993), 109, 1239-1246 nique (Hamill et al, 1981 were not used for experiments. Since the external solution was Na+-free, a possible involvement of Na+-dependent K+ current (Coraboeuf & Carmeliet, 1982;Escande et al, 1987;Bader et al, 1990) was eliminated. Ca2+ currents were eliminated by 5011M Cd2+ which completely blocked Ca2+ currents in rat DRG Voltage (mV)…”

Section: Electrical Recordingmentioning

confidence: 99%

Differential inhibition of a transient K+ current by chlorpromazine and 4‐aminopyridine in neurones of the rat dorsal root ganglia

Ogata

Tatebayashi

1993

British J Pharmacology

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1 K+ currents were recorded from neurones of the newborn rat cultured dorsal root ganglia, by a whole cell variation of the patch-clamp technique. 2 Chlorpromazine (CPZ), a neuroleptic, reversibly reduced the amplitude of the transient K+ current (referred to as 'IT' hereafter) with a dissociation constant (Kd) of 4.5 j4M. The inhibition of the delayed rectifier K+ current (IDR) was much less potent (Kd, 120 l4M). CPZ (100 tM) had no effect on the inward rectifier K+ current.3 The blocking action of CPZ on IT was about seven times more potent than that of 4-aminopyridine (4-AP) which had a Kd of 31 gM. The inhibition of IT followed one-to-one binding stoichiometry with both drugs. 4 The decay time course of IT was not affected by CPZ, whereas 4-AP markedly accelerated the decay phase of IT.5 The steady-state inactivation curve of IT was shifted in the negative direction (about 5 mV) by CPZ, whereas the curve was shifted in the positive direction (about 13 mV) by 4-AP. 6 The recovery from inactivation as measured by a conventional double pulse protocol was described by two exponential components in the control solution. CPZ markedly reduced the first component and slowed down the recovery from inactivation. In contrast, in the presence of 4-AP, the peak amplitude of IT was rather increased by a preceding IT possibly through voltage-dependent unbinding of 4-AP molecules.7 These results indicate that CPZ has a preferential blocking action on IT and the mechanism underlying this block is markedly different from the mechanism underlying the blocking action of 4-AP.

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“…), anesthetized [15][16][17][18][19][20] minutes later with a-chloralose (100 mg/kg i.v. ), and supplemented as needed.…”

Section: Methods Surgical Preparationmentioning

confidence: 99%

T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Implications with respect to phenomenon of cardiac 'memory'.

Balzo

Rosen

1992

Circulation

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BACKGROUND Cardiac "memory" refers to changes in T wave polarity induced by ventricular pacing that persist long after resumption of normal atrioventricular conduction. METHODS AND RESULTS We studied the occurrence and mechanism of T wave changes in the open-chest anesthetized dog subjected to three discontinuous 20-minute periods of right ventricular pacing. ECG changes were recorded in the standard limb leads during normal conduction (prepacing) and three trains (T1, T2, and T3) of right ventricular pacing at a rate 50% higher than normal (pacing), each followed by a period of normal conduction (postpacing) lasting as long as necessary for T wave changes to return to control values. During each of these phases, heart rate, QRS, corrected QT (QTc) duration, and T wave amplitude were measured. In the first group (control), T wave inversions occurred during normal atrioventricular conduction after a period of right ventricular pacing. These T wave anomalies appeared in the absence of any change in heart rate, QRS, or QTc duration. The magnitude of the T wave amplitude change was significantly greater after each successive pacing period. Furthermore, the changes in T wave morphology persisted for a longer period after each successive pacing train. In a second experimental group, lidocaine, which depresses the sodium window current, was administered to six dogs that were subjected to the same pacing protocol. Lidocaine decreased the QTc interval and prolonged QRS duration but did not alter the magnitude of changes in T wave amplitude and time to recovery described in control animals during the three postpacing intervals. In contrast, in the third group, 4-aminopyridine, a drug that blocks the transient outward current (ito), abolished the changes in T wave morphology that occurred during any postpacing interval. CONCLUSIONS These results demonstrate that the manifestation of cardiac memory in the in situ dog heart is not altered by lidocaine but is abolished by 4-aminopyridine. Thus, cardiac memory may be based on a physiological property of the myocardium that is related to specific K+ channels.

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Existence of two transient outward currents in sheep cardiac Purkinje fibers

Cited by 212 publications

References 35 publications

Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle

Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle

Differential inhibition of a transient K+ current by chlorpromazine and 4‐aminopyridine in neurones of the rat dorsal root ganglia

T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Implications with respect to phenomenon of cardiac 'memory'.

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