Mechanisms underlying the modulation of arrhythmogenic events by components of ischemia in guinea pig cardiac myocytes

1994 ◽  
Vol 72 (4) ◽  
pp. 382-393 ◽  
Author(s):  
Qi-Ying Liu ◽  
Mario Vassalle
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Voltage Clamp ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Resting Potential ◽  
Spontaneous Discharge ◽  
High K ◽  
Voltage Dependent ◽  
Dependent Mechanism

The effects of some components of ischemia on the oscillatory (Vos) and nonoscillatory (Vex) potentials and respective currents (Ios and Iex), as well as their mechanisms, were studied in guinea pig isolated ventricular myocytes by means of a single-microelectrode, discontinuous voltage clamp method. Repetitive activations induced not only Vos and Ios, but also Vex and Iex. A small decrease in resting potential caused an immediate increase in Vos followed by a gradual increase due to the longer action potential. Immediate and gradual increases in Ios also occurred during voltage clamp steps. A small depolarization increased Vos and Vex, and facilitated the induction of spontaneous discharge by fast drive. At Vh where INa is inactivated, depolarizing steps induced larger Ios and Iex, indicating the importance of the Na-independent Ca loading. High [K]odecreased the resting potential, but also Vos, Vex, Ios, Iex, and ICa. In high [K]o, depolarization still increased Vos and Vex. Norepinephrine (NE) enhanced Vos and Vex, and also Ios and Iex, during voltage clamp steps. High [K]o antagonized NE effects, and NE those of high [K]o. In conclusion, on depolarization, Vos and Ios immediately increase through a voltage-dependent mechanism; and then Vos and Ios gradually increase, apparently through an increased Ca load related to the longer action potentials and the Na–Ca exchange. The depolarization induced by Vex may contribute to increase Vos size. Vos and Vex are similarly influenced by different procedures that modify Ca load. The arrhythmogenic events are enhanced by the simultaneous presence of depolarization, faster rate, or NE. Instead, high [K]o decreases Vos and Vex by decreasing ICa and opposes the effects of NE. The voltage clamp results show that potentiation and antagonism between different components of ischemia are due primarily to changes in Ca loading and not to changes in action potential configuration.Key words: ischemia, arrhythmias, oscillatory and nonoscillatory potentials and currents, norepinephrine, potassium.

Effects of estrogen on action potential and membrane currents in guinea pig ventricular myocytes

1999 ◽  
Vol 277 (2) ◽  
pp. H826-H833 ◽  
Author(s):  
Seiko Tanabe ◽  
Toshio Hata ◽  
Masayasu Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Action Potentials ◽  
Voltage Dependence ◽  
Ventricular Myocytes ◽  
Membrane Currents ◽  
Patch Clamp Technique ◽  
17Β Estradiol ◽  
Electrophysiological Effects ◽  
Ionic Basis

To explore a possible ionic basis for the prolonged Q-T interval in women compared with that in men, we investigated the electrophysiological effects of estrogen in isolated guinea pig ventricular myocytes. Action potentials and membrane currents were recorded using the whole cell configuration of the patch-clamp technique. Application of 17β-estradiol (10–30 μM) significantly prolonged the action potential duration (APD) at 20% (APD20) and 90% repolarization (APD90) at stimulation rates of 0.1–2.0 Hz. In the presence of 30 μM 17β-estradiol, APD20 and APD90 at 0.1 Hz were prolonged by 46.2 ± 17.1 and 63.4 ± 11.7% of the control ( n = 5), respectively. In the presence of 30 μM 17β-estradiol the peak inward Ca2+ current ( I CaL) was decreased to 80.1 ± 2.5% of the control ( n = 4) without a shift in its voltage dependence. Application of 30 μM 17β-estradiol decreased the rapidly activating component of the delayed outward K+ current ( I Kr) to 63.4 ± 8% and the slowly activating component ( I Ks) to 65.8 ± 8.7% with respect to the control; the inward rectifier K+ current was barely affected. The results suggest that 17β-estradiol prolonged APD mainly by inhibiting the I Kcomponents I Krand I Ks.

Changes in cytosolic calcium monitored by inward currents during action potentials in guinea-pig ventricular cells

1989 ◽  
Vol 238 (1291) ◽  
pp. 171-188 ◽  
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Voltage Clamp ◽  
Action Potentials ◽  
Single Cells ◽  
Calcium Transient ◽  
Cytosolic Calcium ◽  
Time To Peak ◽  
Ventricular Cells ◽  
In Cells

Action potentials were recorded from single cells isolated from guinea-pig ventricular muscle. Contraction was measured with an optical technique. Tail currents thought to be activated by cytosolic calcium were recorded when action potentials were interrupted by application of a voltage-clamp. A family of tail currents was recorded by interrupting the action potential at various times after the upstroke. The envelope of tail current amplitudes was taken as an index of changes in cytosoli calcium. Con­sistent with this interpretation, tail currents were negligible following intracellular loading with the calcium chelator BAPTA to suppress calcium transients. The cytosolic calcium transient estimated from the envelope of tails reached a peak approximately 50 ms after the upstroke of the action potential, and fell close to diastolic levels before repolarization was com­plete; 10 mM caffeine delayed the time to peak contraction, and caused a prolongation of the cytosolic calcium transient estimated from the envelope of tail currents. Caffeine also induced the appearance of a distinct late plateau phase of the action potential. Intracellular BAPTA suppressed the late plateau, contraction and tail currents in cells exposed to caffeine. Exposure to caffeine increased the time constant for decay of tail currents (from approximately 35 to 70 ms). When action potentials were greatly abbreviated by interruption with a voltage-clamp, a pro­gressive decline occurred in the subsequent three contractions and tail currents. There was a progressive reversal of these effects over four responses when the full action potential duration was restored. None of these effects was observed in cells exposed to caffeine. Calcium-activated tail currents appear to be a useful qualitative index of changes in cytosolic calcium. The observations are consistent with the suggestion that cytosolic calcium is reduced during the plateau by a combination of calcium extrusion through Na–Ca exchange and calcium uptake into caffeine-sensitive stores. It also appears that reduction of stores loading during abbreviated action potentials reduces subsequent contraction in cells not exposed to caffeine.

L-364,373 (R-L3) enantiomers have opposite modulating effects on IKs in mammalian ventricular myocytes

2013 ◽  
Vol 91 (8) ◽  
pp. 586-592 ◽  
Author(s):  
Claudia Corici ◽  
Zsófia Kohajda ◽  
Attila Kristóf ◽  
András Horváth ◽  
László Virág ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Guinea Pig ◽  
Action Potential ◽  
Right Ventricular ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Ventricular Arrhythmias ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Whole Cell Patch Clamp

Activators of the slow delayed rectifier K+ current (IKs) have been suggested as promising tools for suppressing ventricular arrhythmias due to prolongation of repolarization. Recently, L-364,373 (R-L3) was nominated to activate IKs in myocytes from several species; however, in some studies, it failed to activate IKs. One later study suggested opposite modulating effects from the R-L3 enantiomers as a possible explanation for this discrepancy. Therefore, we analyzed the effect of the RL-3 enantiomers on IKs in ventricular mammalian myocytes, by applying standard microelectrode and whole-cell patch-clamp techniques at 37 °C. We synthesized 2 substances, ZS_1270B (right) and ZS_1271B (left), the 2 enantiomers of R-L3. In rabbit myocytes, ZS_1270B enhanced the IKs tail current by approximately 30%, whereas ZS_1271B reduced IKs tails by 45%. In guinea pig right ventricular preparations, ZS_1270B shortened APD90 (action potential duration measured at 90% repolarization) by 12%, whereas ZS_1271B lengthened it by approximately 15%. We concluded that R-L3 enantiomers in the same concentration range indeed have opposite modulating effects on IKs, which may explain why the racemic drug R-L3 previously failed to activate IKs. ZS_1270B is a potent IKs activator, therefore, this substance is appropriate to test whether IKs activators are ideal tools to suppress ventricular arrhythmias originating from prolongation of action potentials.

Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes

1990 ◽  
Vol 258 (4) ◽  
pp. H931-H938 ◽  
Author(s):  
J. Meszaros ◽  
A. J. Pappano
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Membrane Depolarization ◽  
Time Dependent ◽  
Resting Potential ◽  
Neuraminidase Treatment ◽  
Single Ventricular Myocytes ◽  
Electrophysiological Effects

In isolated guinea pig ventricular myocytes, L-palmitoylcarnitine (L-PC) produced concentration- and time-dependent changes of resting potential (RP) and action potential duration at 50% repolarization (APD50). At 10(-8) to 10(-6) M, L-PC increased APD50 without changing RP. At 10(-5) M, the amphiphile initially increased (0-10 min) and eventually decreased (greater than 10 min) APD50; the membrane depolarized when APD50 decreased. Additionally, transient depolarizations (TDs) were consistently induced in 10(-5) M L-PC within 10 min, and TD amplitude progressively increased with continued exposure to L-PC. The TDs induced in L-PC were augmented by membrane depolarization, elevated extracellular Ca2+ concentration ([Ca2+]o), and increased number of stimuli. Elevated [Ca2+]o or neuraminidase treatment also allowed TDs. In neuraminidase, the changes of RP, APD50, and TD amplitude were qualitatively similar to those seen with L-PC. These results are consistent with the hypothesis that 10(-5) M L-PC causes intracellular Ca2+ overload. The blockade of L-PC and neuraminidase-induced TDs by ryanodine is consistent with the intracellular Ca2+ overload hypothesis.

Ionic basis of the action potential of guinea pig gallbladder smooth muscle cells

1993 ◽  
Vol 265 (6) ◽  
pp. C1552-C1561 ◽  
Author(s):  
L. Zhang ◽  
A. D. Bonev ◽  
M. T. Nelson ◽  
G. M. Mawe
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Action Potential ◽  
Smooth Muscle Cells ◽  
Action Potentials ◽  
Outward Current ◽  
Muscle Cells ◽  
Tetraethylammonium Chloride ◽  
Voltage Dependent ◽  
Calcium Activated Potassium Channels

Smooth muscle cells in the intact guinea pig gallbladder had a resting membrane potential of about -45 mV and had spontaneous action potentials that consisted of a rapid depolarization, a transient repolarization, a plateau phase, and a complete repolarization. These action potentials lasted approximately 570 ms and occurred at a frequency of approximately 0.4 Hz. Action potentials were abolished by the dihydropyridine (DHP)-sensitive Ca2+ channel blocker nifedipine (1.0 microM) and were enhanced by the DHP-sensitive Ca2+ channel agonist BAY K 8644 (0.5 microM). The K+ channel blockers tetraethylammonium chloride (5.0 mM) and 4-aminopyridine (4-AP; 2.0 mM) prolonged the action potential, whereas charybdotoxin (100 nM), a blocker of calcium-activated potassium channels, had no effect. Whole cell currents were characterized in enzymatically isolated smooth muscle cells from the same preparation. 4-AP, a blocker of voltage-dependent K+ channels, suppressed 70% of the outward current at 0 mV. Charybdotoxin (100 nM) reduced an additional 15% of the current at 0 mV. Single calcium-activated potassium channels were identified. The potential for half-activation of these channels, at a cytosolic Ca2+ concentration of 100 nM, was 66.8 mV. A fivefold increase in cytosolic Ca2+ resulted in a shift of the activation curve by -53 mV. External tetraethylammonium chloride (200 microM) reduced the mean single channel current by 48% at 0 mV. The whole cell outward current was abolished by replacement of intracellular K+ for Cs+. Ca2+ currents were inhibited by nifedipine and were increased by BAY K 8644. We conclude that DHP-sensitive voltage-dependent Ca2+ channels are responsible for the depolarization of the action potentials and that the repolarization is due to primarily 4-AP-sensitive K+ current.

Effect of [NO3] on atrial action potentials and contraction as modified by [Na] and [Ca]

1962 ◽  
Vol 202 (5) ◽  
pp. 950-956 ◽  
Author(s):  
Nancy S. Peterson ◽  
George A. Feigen
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Nutrient Medium ◽  
Action Potentials ◽  
Initial Phase ◽  
Resting Potential ◽  
Terminal Phase ◽  
Transmembrane Potentials ◽  
Conventional Methods ◽  
Guinea Pig Atria

Transmembrane potentials and contractility were measured in driven guinea pig atria according to conventional methods. The effects of nitrate were studied by substituting 40, 60, 80, and 100% of the chlorides with nitrates, and the influence of Ca and Na was determined by varying their ratio in the presence of 40% nitrate. The magnitudes of the resting potential, action potential, and overshoot were reversibly reduced; the rate of depolarization slowed; and the amplitude of contraction decreased as the proportion of nitrate to chloride was increased in the nutrient medium. In general, the initial phase of the repolarization was shortened, but the terminal phase was slowed. The duration of irresponsiveness was prolonged, and the maximum following frequency was reduced by nitrate. Calcium appeared to antagonize the deleterious effects of nitrate on all of the parameters except the resting potential, the negative afterpotential, and the irresponsive period.

Transmembranal Action Potentials From Pregnant Uterus

1956 ◽  
Vol 187 (2) ◽  
pp. 338-340 ◽  
Author(s):  
J. Walter Woodbury ◽  
Donald M. McIntyre
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Guinea Pigs ◽  
Action Potentials ◽  
Resting Potential ◽  
Pregnant Uterus ◽  
Uterine Muscle ◽  
Order Of Magnitude ◽  
The Mean ◽  
First Time

For the first time overshooting action potentials of pregnant guinea pig uterus have been recorded intracellularly. Flexibly mounted ultramicroelectrodes were used. The largest action potential (AP) seen was 48 mv with an associated resting potential (RP) of 38 mv. The mean of 129 measurements of RP in four guinea pigs was 32.6 mv. The mean of 86 AP's was 21.9 mv. Although overshoot was seen only occasionally, the action potentials were always of the same order of magnitude as the resting potentials. It seems probable that the excitable mechanisms of uterine muscle though labile and variable are closely similar to those of other tissues.

Sodium and calcium currents in acutely dissociated neurons from rat suprachiasmatic nucleus

1993 ◽  
Vol 70 (4) ◽  
pp. 1692-1703 ◽  
Author(s):  
R. C. Huang
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Firing Rate ◽  
Voltage Clamp ◽  
Suprachiasmatic Nucleus ◽  
Time Constant ◽  
Action Potentials ◽  
Calcium Currents ◽  
Resting Potential ◽  
Low Threshold

1. Neurons were acutely dissociated from the suprachiasmatic nucleus (SCN) of adult rats and studied with whole-cell and perforated-patch recordings at room temperature. 2. Acutely dissociated SCN neurons had spherical cell bodies of 12 microns in average diameter. The recorded cells were randomly selected and had either no process (38%), one (41%), two (19%), or three processes (2%). They had a resting potential of about -60 mV, an input resistance of approximately 5 G omega, and a cell capacitance of approximately 7 pF. 3. The dissociated neurons had variable spontaneous firing rates, typically (76%) < 1 Hz. 4. Under current clamp, continuous current injection elicited repetitive action potentials. 1 microM tetrodotoxin (TTX) reduced the amplitudes of the action potentials as well as the firing rate, whereas 200 microM Cd2+ stopped repetitive firing altogether. Action potentials were completely eliminated with Cd2+ and TTX present. These results suggest that both Na+ and Ca2+ contribute to the action potential in these cells. 5. With 200 microM Cd2+ present to block calcium currents, a train of brief depolarizing pulses could still elicit repetitive sodium action potentials, but these became attenuated at stimulating frequencies as low as 1 Hz. 6. Under voltage clamp, the sodium current was activated at about -40 mV and peaked at about -10 mV. It inactivated with a time constant of approximately 0.5 ms at 0 mV, and in steady state the current was half-inactivated at about -60 mV. Recovery of the current from inactivation showed two very different phases with time constants of approximately 30 and 600 ms at -60 mV. The slow phase was probably responsible for the very low firing rate of the sodium action responsible for the very low firing rate of the sodium action potential. 7. In the absence of external sodium, depolarization-activated calcium action potentials were preferentially blocked by 20 microM Cd2+, whereas a posthyperpolarizing depolarizing (or anode break) was preferentially reduced by 100 microM Ni2+. These differential effects hinted at the presence of both low-threshold and high-threshold calcium currents in these cells. 8. Voltage-clamp experiments confirmed the presence of a low-threshold, transient calcium current that was activated by depolarizations above -70 mV. It inactivated with a time constant of approximately 25 ms between -50 and -30 mV. Steady-state inactivation was half-complete at about -90 mV and complete at about -70 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

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