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Results for “Action Potentials”

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PubMed1968

The flash-triggering action potential of the luminescent dinoflagellate Noctiluca.

The action potential which elicits luminescence in Noctiluca is recorded from the flotation vacuole as a transient all-or-none hyperpolarization in response to either local or general application of inward (bath to vacuole) current. Experiments were performed to determine whether the unorthodox polarities of both the stimulus current and the potential response resulted from uncommon bioelectric mechanisms or from special morphological features of this species. The findings all indicate that the action potential belongs to the familiar class of responses which have their origin in voltage- and time-dependent selective increases in membrane permeability, and that morphological factors account for the observed deviations from normal behavior. Both the stimulus and the response have orthodox polarities provided the vacuole is designated as an "external" extracytoplasmic compartment. Differential recording between vacuole and cytoplasm showed that the action potential occurs across the vacuolar membrane, with the cytoplasmic potential, which at rest is negative with respect to the vacuole, overshooting zero and reversing sign to become transiently electropositive. The rising phase of the action potential therefore depends on active current flow through the vacuolar membrane from the vacuole into the cytoplasm. Propagation of the action potential over the subspherical cell from the locus of stimulation is thought to depend largely on the core conductor properties of the thin perivacuolar shell of cytoplasm which is bounded on its inner surface by the excitable membrane and on its outer surface by inexcitable membranes.

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PubMed1986

Effect of the blocked inactivation of sodium channels on intracellular and extracellular action potentials from isolated frog muscle fibres.

The intra- and extracellular action potentials of isolated frog muscle fibres, treated with ATX II for blocking sodium inactivation, are investigated. In concentrations of 0.1 to 0.5 X 10(-6) M, ATX II leads to a considerable change of the repolarization phase of the intracellular potential, with a tendency toward achieving a plateau-type potential. In addition to the intracellular action potentials, extracellular action potentials were also recorded from the same fibres. Immediately next to the fibre membrane and at a small radial distance the extracellular potentials did not manifest essential differences compared with recordings under normal physiological conditions. Conclusions are reached about the influence of the blocked Na-inactivation on the intra- and extracellular action potentials of muscle fibres.

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PubMed1998

Severe and early alteration of action potential during acute cardiac rejection in rats.

INTRODUCTION: Alteration of cardiac action potential and its adaptation to heart rate could contribute to cardiac dysfunction and arrhythmias during acute cardiac rejection. METHODS AND RESULTS: Heterotopic heart transplantation was performed in allogeneic and syngeneic rats in which the action potentials of right and left ventricles were measured at 1, 2.5, 3.3, and 5.7 Hz successively using standard microelectrode techniques and compared with nontransplanted hearts. For each frequency, we measured action potential amplitude, action potential duration, transmembrane resting potential, and Vmax. In the right ventricle, at 1 Hz in the presence of rejection (n = 40), a significant increase was observed in action potential duration at 20%, 50%, and 70% repolarization (82.5%, 75.6%, and 70.8%, respectively) and in action potential amplitude (+17.9 mV), and the resting potential was decreased (-5.3 mV). A lack of adaptation of action potential duration to the driving frequency was observed in the rejecting heart group in contrast to controls (n = 20) and nonrejecting hearts (n = 13). Similar results were observed in the left ventricle and surprisingly in the native hearts (n = 11) of recipients with allografted rejecting hearts in the abdominal position. CONCLUSION: Action potential and its adaptation to the driving frequency is considerably altered during acute rejection. A humoral factor could contribute to cardiac dysfunction.

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PubMed1981

Membrane conductance and action potential of a regenerating axonal tip.

The electrical membrane properties of axotomized and regenerating giant axons from the nerve cord of the cockroach Periplaneta americana were studied. Immediately after axotomy there was a decrease in resting potential, input resistance, and action potential amplitude near the cut end. This decrease was followed by the disappearance of the sodium-dependent action potential; an increase in the resting membrane conductance to K+, Na+, and Ca2+; and the appearance of a calcium-dependent action potential.

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PubMed1983

The development of action potentials in cultures of explanted cortical neurons from chick embryos.

Action potentials of explanted cortical neurons from 7- to 9-day chick embryos were investigated at different stages during culturing. The maximum rates of rise of action potentials gradually increased and reached a plateau level at about 1 month in culture. Action potentials were resistant to 10(-7) g/ml tetrodotoxin (TTX) at early stages, became sensitive to TTX in an age-dependent manner, and almost all action potentials were blocked by this concentration of TTX after 25 days. However, 10(-5) g/ml TTX suppressed action potentials at early stages. When action potentials were suppressed by TTX, impulses could still be obtained from immature neurons following addition of 10 mM Ca2+ to the saline. This effect was not observed in mature neurons. The application of 10 mM Mn2+ frequently enhanced action potentials in immature neurons. This effect was not blocked by TTX (10(-5) g/ml) or the removal of external Na+. These results suggest that action potentials in immature neurons depend on Ca2+ and Na+, that Mn2+ can pass through Ca channels, that the sensitivity to TTX develops as the contribution by Na+ becomes greater, and that the contribution by Ca2+ diminishes during maturation.

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PubMed1996

Propagation of action potentials in the dendrites of neurons from rat spinal cord slice cultures.

1. We examined the propagation of action potentials in the dendrites of ventrally located presumed motoneurons of organotypic rat spinal cord cultures. Simultaneous patch electrode recordings were made from the dendrites and somata of individual cells. In other experiments we visualized the membrane voltage over all the proximal dendrites simultaneously using a voltage-sensitive dye and an array of photodiodes. Calcium imaging was used to measure the dendritic rise in Ca2+ accompanying the propagating action potentials. 2. Spontaneous and evoked action potentials were recorded using high-resistance patch electrodes with separations of 30-423 microm between the somatic and dendritic electrodes. 3. Action potentials recorded in the dendrites varied considerably in amplitude but were larger than would be expected if the dendrites were to behave as passive cables (sometimes little or no decrement was seen for distances of > 100 microm). Because the amplitude of the action potentials in different dendrites was not a simple function of distance from the soma, we suggest that the conductance responsible for the boosting of the action potential amplitude varied in density from dendrite to dendrite and possibly along each dendrite. 4. The dendritic action potentials were usually smaller and broader and arrived later at the dendritic electrode than at the somatic electrode irrespective of whether stimulation occurred at the dendrite or soma or as a result of spontaneous synaptic activity. This is clear evidence that the action potential is initiated at or near the soma and spreads out into the dendrites. The conduction velocity of the propagating action potential was estimated to be 0.5 m/s. 5. The voltage time courses of previously recorded action potentials were generated at the soma using voltage clamp before and after applying 1 microM tetrodotoxin (TTX) over the soma and dendrites. TTX reduced the amplitude of the action potential at the dendritic electrode to a value in the range expected for dendrites that behave as passive cables. This indicates that the conductance responsible for the actively propagating action potentials is a Na+ conductance. 6. The amplitude of the dendritic action potential could also be initially reduced more than the somatic action potential using 1-10 mM QX-314 (an intracellular sodium channel blocker) in the dendritic electrode as the drug diffused from the dendritic electrode toward the soma. Furthermore, in some cases the action potential elicited by current injection into the dendrite had two components. The first component was blocked by QX-314 in the first few seconds of the diffusion of the blocker. 7. In some cells, an afterdepolarizing potential (ADP) was more prominent in the dendrite than in the soma. This ADP could be reversibly blocked by 1 mM Ni2+ or by perfusion of a nominally Ca2+-free solution over the soma and dendrites. This suggests that the back-propagating action potential caused an influx of Ca2+ predominantly in the dendrites. 8. With the use of a voltage-sensitive dye (di-8-ANEPPS) and an array of photodiodes, the action potential was tracked along all the proximal dendrites simultaneously. The results confirmed that the action potential propagated actively, in contrast to similarly measured hyperpolarizing pulses that spread passively. There were also indications that the action potential was not uniformly propagated in all the dendrites, suggesting the possibility that the distribution of Na+ channels over the dendritic membrane is not uniform. 9. Calcium imaging with the Ca2+ fluorescent indicator Fluo-3 showed a larger percentage change in fluorescence in the dendrites than in the soma. Both bursts and single action potentials elicited sharp rises in fluorescence in the proximal dendrites, suggesting that the back-propagating action potential causes a concomitant rise in intracellular calcium concentration...

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PubMed1984

Mechanism of reduction of action potential duration of ventricular myocardium by exogenous lactate.

Shortening of the action potential duration and the attendant reduction of refractory period in regional myocardial ischaemia might set the stage for the genesis and re-entry of ectopic impulses. We investigated the mechanism by which neutral lactate shortens the action potential duration since lactate accumulates highest in regions where coronary flow is lowest after experimental coronary artery occlusion. In preliminary experiments (unpublished) when 10 mM of L(+)-Na lactate was substituted for glucose (10 mM), action potential duration shortened in the majority of guinea pig papillary muscles. In some of the muscles, the action potential duration lengthened. When the perfusate contained neither glucose nor lactate (i.e. substrate free) action potential duration shortened in the majority of experiments. As mechanism, we supposed that the relatively high contraction rate of the preparations (120/min) could exhaust glycogen stores thereby limiting glycolysis and shortening the action potential duration. Thus variable action potential duration during lactate or substrate-free superfusion, might be explained by a corresponding variability of pre-existing glycogen stores. Therefore, in the present study we attempted to reduce the demand on glycogen stores by decreasing the contraction rate to 30/min. In the latter preparation, when the diastolic (passive) tension was completely normal, lactate (10 mM) shortened the action potential duration by 30%, whereas the action potential duration was not altered during substrate free superfusion. We then explored the possibility that lactate shortened the action potential duration by inhibition of glycolysis. First, muscles were made to perform external work by increasing passive tension to the peak of the active length-tension curve.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Sensory and mixed nerve action potential temporal dispersion in median neuropathy at the wrist.

This retrospective pilot study was undertaken to help determine the usefulness of measuring sensory nerve action potential and mixed nerve action potential temporal dispersion in median neuropathy at the wrist (MNW; i.e., carpal tunnel syndrome). The records were reviewed for 34 patients who were referred to an electrodiagnostic medicine laboratory with normal antidromic median sensory nerve action potential (recording from the index finger), median transcarpal mixed nerve action potential, and ulnar transcarpal mixed nerve action potential peak distal latencies (NO group) and 29 patients with prolongation (>2.2 ms) of the left median transcarpal mixed nerve action potential peak distal latency or relative prolongation of this response (>0.4 ms) compared with the ipsilateral normal ulnar transcarpal mixed nerve action potential peak distal latency (MNW group). By using the time difference between onset and negative peak as a measure of waveform temporal dispersion, mean +/- standard deviation of the median transcarpal mixed nerve action potential time difference for the MNW group (0.57 +/- 0.15 ms) was found to be greater than the NO group (0.44 +/- 0.09 ms; P < 0.01). No statistically significant differences were found for the median sensory nerve action potential time difference between the two groups or between the subgroup of MNW patients with concurrent prolongation of the median sensory nerve action potential peak distal latency and the NO group. These findings suggest that increased median transcarpal mixed nerve action potential temporal dispersion may occur in association with median transcarpal mixed nerve action potential peak distal latency prolongation in MNW. The small magnitude of this increase, however, makes the clinical usefulness of this observation unclear.

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PubMed1996

Effects of chronic hypoxia on the developmental changes in action potential of cultured neonatal rat ventricular myocytes.

The action potentials of rat ventricular myocytes are known to become progressively shortened within several weeks after birth. We studied the effects of long-term exposure to hypoxia on these developmental changes in cardiac action potentials. Single ventricular myocytes isolated from day-old neonatal rat hearts were cultured in normoxic conditions (21% O2) for more than 15 days. To test the influence of long-term exposure to hypoxia, O2 tension was lowered to 7.5% in some cells at day 6. Action potentials were measured at day 5 and day 15 in both the normoxic and hypoxic groups. Under normoxic conditions, action potential durations decreased by 44% between day 5 and day 15, while cell capacitance doubled (n=10-11). Under hypoxic conditions, action potential durations decreased slightly by 16% (n=6). This shortening was significantly attenuated when compared to that observed during normoxic conditions. Cell capacitance was not altered under the hypoxic conditions. These results suggest that 1) shortening of the action potential during normoxic culturing is prevented under hypoxic conditions, and 2) cell capacitance as seen in normoxic conditions is unaffected by hypoxic culturing.

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PubMed1998

GABA-dependent generation of ectopic action potentials in the rat hippocampus.

Intracellular recordings from CA3 pyramidal cells of rat hippocampus in a slice preparation revealed the occurrence of interictal epileptiform discharges and synchronous GABA-mediated potentials during application of 4-aminopyridine (4AP, 50 micrometer). The synchronous GABA-mediated potential consisted of a sequence of early hyperpolarization, long-lasting depolarization (LLD), and late hyperpolarization. Action potentials of variable amplitude occurred at the peak of the early hyperpolarization and during the LLD rising phase (48 of 64 cells); they were not prevented by membrane hyperpolarization and displayed inflections that were reminiscent of the initial segment-somatodendritic (IS-SD) fractionation. Interictal discharges were blocked by excitatory amino acid receptor antagonists, while both GABA-mediated potentials and action potentials of variable amplitude continued to occur (n = 10). The latter events were still recorded in the presence of the GABAB receptor antagonist CGP-35348 (0.5-1 mm, n = 4), but were abolished by the GABAA receptor antagonist bicuculline methiodide (BMI, 10 micrometer, n = 5). Localized application of BMI (20 micrometer, n = 6) or tetrodotoxin (TTX, 5 micrometer, n = 3) to the CA1 stratum radiatum blocked the variable amplitude action potentials; these effects were not seen when BMI (n = 4) or TTX (n = 4) were applied to the CA3 stratum radiatum, although both procedures made LLDs disappear. Our findings indicate that action potentials of variable amplitude recorded from CA3 pyramidal cells in the 4AP model are generated at or near the terminal region of the Schaffer collaterals and that they represent TTX-sensitive ectopic events. These action potentials are generated at this site by a BMI-sensitive (and thus GABAA-mediated) mechanism. We propose that the ectopic action potentials reflect an increased excitability of axon terminals that is presumably caused by [K+]o elevations associated with the 4AP-induced synchronous GABA-mediated potential.

4-Aminopyridine↗

PubMed2001

Differences in the size of the somatic action potential overshoot between nociceptive and non-nociceptive dorsal root ganglion neurones in the guinea-pig.

Intracellular action potentials evoked by dorsal root stimulation were intracellularly recorded from L6 and S1 dorsal root ganglion neurones in deeply anaesthetised guinea-pigs in vivo. Units were classed as C, Adelta or Aalpha/beta units and as nociceptive, low-threshold mechanoreceptive or unresponsive. Units with membrane potentials of at least -40 mV and action potentials with an amplitude of >20 mV were included. Nociceptive neurones had significantly larger somatic action potential overshoots than low-threshold mechanoreceptors in C, Adelta and Aalpha/beta units. A higher proportion of low-threshold mechanoreceptors than of nociceptors had action potentials that failed to overshoot in all conduction velocity groups. 60% of muscle spindle afferents failed to overshoot. The size of the overshoot was correlated positively with log(10) action potential duration, log(10) action potential rise time, log(10) afterhyperpolarisation duration, action potential amplitude and membrane potential and negatively (weakly) with log(10) conduction velocity.We conclude that nociceptive neurones are more likely to have somatic action potential overshoots than low-threshold mechanoreceptors in any conduction velocity group. This effect was not due to electrode properties or conduction failure at site(s) of failure of action potential regeneration. Differences in overshoot may affect the influence of neuronal firing on cellular processes. If an overshooting action potential is used as a selection criterion, a bias towards nociceptive neurones is likely to occur. An overshooting action potential coupled with a long afterhyperpolarisation or broad action potential may help in identifying sensory neurones as nociceptive.

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PubMed1997

Prolonged sodium channel inactivation contributes to dendritic action potential attenuation in hippocampal pyramidal neurons.

During low-frequency firing, action potentials actively invade the dendrites of CA1 pyramidal neurons. At higher firing rates, however, activity-dependent processes result in the attenuation of back-propagating action potentials, and propagation failures occur at some dendritic branch points. We tested two major hypotheses related to this activity-dependent attenuation of back-propagating action potentials: (1) that it is mediated by a prolonged form of sodium channel inactivation and (2) that it is mediated by a persistent dendritic shunt activated by back-propagating action potentials. We found no evidence for a persistent shunt, but we did find that cumulative, prolonged inactivation of sodium channels develops during repetitive action potential firing. This inactivation is significant after a single action potential and continues to develop during several action potentials thereafter, until a steady-state sodium current is established. Recovery from this form of inactivation is much slower than its induction, but recovery can be accelerated by hyperpolarization. The similarity of these properties to the time and voltage dependence of attenuation and recovery of dendritic action potentials suggests that dendritic sodium channel inactivation contributes to the activity dependence of action potential back-propagation in CA1 neurons. Hence, the biophysical properties of dendritic sodium channels will be important determinants of action potential-mediated effects on synaptic integration and plasticity in hippocampal neurons.

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PubMed1978

Action potentials of embryonic dorsal root ganglion neurones in Xenopus tadpoles.

1. Several classes of action potentials can be distinguished in dorsal root ganglion cells, studied by intracellular recording techniques in Xenopus laevis tadpoles 4.5--51 days old. The ionic basis of the action potential was investigated by changing the ionic environment of the cells and applying various blocking agents. 2. The Ca2+-dependent action potential is a plateau of relatively long duration (mean 8.7 msec). It is unaffected by removal of Na+ but blocked by mM quantities of Co2+. It is present only in small cells. 3. Ca2+/Na+-dependent action potentials. Type I is a spike followed by a plateau or hump of different durations (mean 8.1 msec). The spike is selectively blocked by removal of Na+, leaving the plateau which is in turn blocked by Co2+. It is present in cells of small and intermediate size. Type II is a spike of short duration (mean 2.0 msec) with only an inflection on the falling phase. The spike is blocked by removal of Na+ and no other components can be elicited. The inflection is blocked by Co2+. It is present in cells of all sizes. Type III is similar to type I but is seen only in solutions in which the outward current is blocked. It was observed only very infrequently. 4. Na+-dependent action potentials. Type I a is a short duration spike (mean 1.1 msec). It is abolished by removal of Na+ or addition of tetrodotoxin (TTX), but largely unaffected by Co2+ or La3+. It is present in cells of all sizes. When the outward current channels are blocked and cells exposed to Na+-free solutions, all cells are capable of producing an action potential in which the inward current is carried by divalent cations. Type I b is a spike with a smooth, more slowly falling phase. It has the same pharmacological properties as type I a action potential and is present in cells of small size. 5. Na+-dependent action potentials. Type II is a spike with an inflection on the falling phase (mean duration 3.4 msec). It is prolonged by Co2+ and La3+. Removal of Na+ abolishes the spike but TTX does not block it. It is present in cells of all sizes. The mean resting potential is less than that of cells with Na+-dependent type I action potentials, while the mean input resistance is greater. 6. Tetraethylammonium chloride (TEA) prolongs the different kinds of action potentials. The amount of prolongation varies among cells with a given type of action potential, so that no distinction could be made of the different actionpotential types based on the effect of TEA. 7. The percent of cells with each kind of action potential varies with the developmental age of the animal. The number of cells with Ca2+ and Ca2+/Na+ action potentials decreases with age, while the number of cells with a Na+ type I action potentials increases. The Na+ type II action potential appears only at later stages. 8...

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PubMed1990

Study of the effects and mechanisms of berberine on slow-response action potentials.

The effects of berberine on slow-response action potentials (SAP) of guinea pig papillary muscles were studied. SAP was elicited by histamine in a high concentration of potassium solution (27 mmol). The results showed that berberine (24.5 mumol) was able to increase action potential amplitude, maximum rate of depolarization, action potential duration 50, action potential duration 100 (n = 16, p less than 0.01) and effective refractory period (n = 10, p less than 0.01) of SAP by 6.2%, 21.1%, 50.1%, 47.2% and 92.2%, respectively, but did not affect the resting membrane potential (RMP). To the above parameters, except APD 100, berberine was no longer to induce any significant change by pretreating with propranolol. The results suggested that the effects of berberine on slow-response action potentials were mainly related to the facilitating of slow calcium inward current, which might result from stimulating the beta-adrenoceptor.

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PubMed2001

Differential shunting of EPSPs by action potentials.

Neurons encode information and communicate via action potentials, which are generated following the summation of synaptic events. It is commonly assumed that action potentials reset the membrane potential completely, allowing another round of synaptic integration to begin. We show here that the conductances underlying the action potential act instead as a variable reset of synaptic integration. The strength of this reset is cell type-specific and depends on the kinetics, location, and timing of the synaptic input. As a consequence, distal synapses, as well as inputs mediated by N-methyl-d-aspartate receptor activation, can contribute disproportionately to synaptic integration during action potential firing.

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PubMed1963

A QUANTITATIVE DESCRIPTION OF THE RELATIONSHIP BETWEEN THE AREA OF RABBIT VENTRICULAR ACTION POTENTIALS AND THE PATTERN OF STIMULATION.

Intracellular microelectrodes were used to record action potentials from fibres of the isolated rabbit right ventricle and the areas of the action potentials were measured. The action potential area was found to depend in a reproducible way on the preceding pattern of stimulation. A mathematical model reproducing all the observed changes in the action potential area was developed. In the model the action potential area is taken as a linear function of the product of two time and stimulation dependent variables, M and N. The behaviour of each variable between action potentials is described by the solution of a second order differential equation. During each action potential the variables are assumed to change discontinuously, the magnitudes of the discontinuous changes being given by a set of subsidiary equations. It was found that the behaviour of all the fibres tested was described by the same set of equations, each single fibre being characterized by a set of ten independent constants.

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PubMed1998

Na+-Dependent neuritic spikes initiate Ca2+-dependent somatic plateau action potentials in insect dorsal paired median neurons.

The origin of plateau action potentials was studied in short-term cultures of dorsal paired median (DPM) neurons dissociated from the terminal abdominal ganglion of the cockroach, Periplaneta americana. Spontaneous plateau action potentials were recorded by intracellular microelectrodes in cell bodies that had neurite stumps. These action potentials featured a fast initial depolarization followed by a plateau. However, only fast spikes of short duration were observed when the cell was hyperpolarized from the resting membrane potential. These two different components of the action potentials could be separated by applying depolarizing current pulses from a hyperpolarized holding potential. Application of 200 nM tetrodotoxin (TTX) abolished both fast and slow phases, but depolarization to the original resting potential by steady current injection triggered slow monophasic action potentials that could be blocked by 3 mM CoCl2. In contrast, DPM neurons without neurites were not spontaneously active. In these cells, calcium-dependent slow monophasic action potentials were only recorded immediately after impalement or with current pulse stimulation. Immunocytochemical observations showed that dorsal unpaired median (DUM) neuron cell bodies, which are known to exhibit spontaneous sodium-dependent action potentials, reacted with an antibody directed against a synthetic peptide corresponding to the SP19 segment of voltage-activated sodium channels. In contrast, the antibody did not stain DPM neuron cell bodies but gave intense, patchy staining only in the neurite. Whole cell patch-clamp experiments performed on isolated DPM neuron cell bodies without a neurite revealed the presence of an inward current that did not inactivate completly within the duration of the test pulse. This current was insensitive to both 100 nM TTX and sodium-free saline. It was defined as a high-voltage-activated calcium current according to its high threshold of activation (-30 mV) and its sensitivity to 1 mM CdCl2 and 100 nM omega-conotoxin GVIA. Our findings demonstrate that spontaneous sodium-dependent spikes arising from the neurite are required to initiate slow somatic calcium-dependent action potentials in DPM neurons.

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PubMed1999

Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes.

The mechanism of action potential abbreviation caused by increasing rate in human ventricular myocytes is unknown. The present study was designed to determine the potential role of Ca2+ current (ICa) in the rate-dependent changes in action potential duration (APD) in human ventricular cells. Myocytes isolated from the right ventricle of explanted human hearts were studied at 36 degreesC with whole cell voltage and current-clamp techniques. APD at 90% repolarization decreased by 36 +/- 4% when frequency increased from 0.5 to 2 Hz. Equimolar substitution of Mg2+ for Ca2+ significantly decreased rate-dependent changes in APD (to 6 +/- 3%, P < 0.01). Peak ICa was decreased by 34 +/- 3% from 0.5 to 2 Hz (P < 0.01), and ICa had recovery time constants of 65 +/- 12 and 683 +/- 39 ms at -80 mV. Action potential clamp demonstrated a decreasing contribution of ICa during the action potential as rate increased. The rate-dependent slow component of the delayed rectifier K+ current (IKs) was not observed in four cells with an increase in frequency from 0.5 to 3.3 Hz, perhaps because the IKs is so small that the increase at a high rate could not be seen. These results suggest that reduction of Ca2+ influx during the action potential accounts for most of the rate-dependent abbreviation of human ventricular APD.

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