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Biomedical subjects

A Elizalde

Publications and source records attributed to A Elizalde.

At least 19 recordsLinked to original sources
PubMed2000

Developmental differences in delayed rectifying outward current in feline ventricular myocytes.

In the present work, we found that the delayed rectifying outward potassium current (I(K)) in adult and neonatal cat ventricular myocytes consists of both rapid and slow components, I(Kr) and I(Ks), respectively, which can be isolated pharmacologically. Thus after complete blockade of I(Kr) with dofetilide, the remaining I(Ks) current is homogeneous, as shown by an envelope of tails test. I(Kr) maximum tail current density, measured at -40 mV, was similar in adult and neonatal myocytes. I(Ks) maximum tail current density in neonatal myocytes, measured at -40 mV, was significantly smaller than in adult myocytes. Activation kinetics of I(Kr) and I(Ks) was similar in both age groups. However, the I(Kr) deactivation time course was significantly faster in neonatal than in adult myocytes. Developmental differences in the subunit composition of I(Kr) that display distinctly different deactivation kinetics are suggested.

Aging↗
PubMed1999

Frequency-dependent effects of 4-aminopyridine and almokalant on action-potential duration of adult and neonatal rabbit ventricular muscle.

The effects of 4-aminopyridine (1 mM) and almokalant (1 microM) on action-potential duration of neonatal and adult rabbit ventricular multicellular preparations and plateau membrane currents of single ventricular myocytes were studied. In adult ventricular preparations, 4-aminopyridine increased action-potential duration in a frequency-dependent manner, with a greater effect at low stimulation frequencies ("reverse" use dependence). In neonatal preparations, the increase in action-potential duration by 4-aminopyridine was significantly smaller than in adults, and the effect was frequency independent. Almokalant increased the action-potential duration more in neonatal than in adult myocytes. The effect of almokalant was frequency independent between 0.5 and 2 Hz. The block of transient outward current and delayed rectifier current in single myocytes was quantitatively similar. We propose that differences in the kinetic behavior of the transient outward current between adult and neonatal ventricular preparations, slower inactivation, and recovery from inactivation in adults determine differences in the frequency-dependent changes induced by 4-aminopyridine and almokalant on action-potential duration.

4-Aminopyridine↗
PubMed1996

Characterization of a complex translocation [t(4;9;22)(p16;q34;q11)] in chronic myelogenous leukemia by fluorescence in situ hybridization technique.

A patient was referred with a high leukocyte count and diagnosed with chronic myelogenous leukemia (CML). Although practically asymptomatic since the time of diagnosis, he had a variable and inconsistent response to treatment. All of his bone marrow cells had a complex, three-way translocation, involving chromosomes 4, 9 and 22. Translocation of chromosome 4 to chromosome 9 was undetectable by routine cytogenetic techniques; however, by the fluorescence in situ hybridization technique, a three-way translocation was identified, 46,XY,t(4;9;22)(p16;q34;q11). Although, other chromosomes are frequently involved in complex or variant translocations with chromosome 9 and 22, participation of chromosome 4 is a very rare event. So far, two previous cases have been described in the literature with translocations involving chromosome 4p16. We present a third case of CML having similar break points whose clinical presentation is unusual.

Allopurinol↗
PubMed1994

Differences in outward currents between neonatal and adult rabbit ventricular cells.

In adult rabbit ventricular preparations, action potential duration is significantly increased when stimulation frequency is increased from 0.1 to 1.0 Hz. In neonatal preparations, a similar change in stimulation frequency produced no significant increase in action potential duration. To identify the ionic basis for this difference, we studied different outward currents in single myocytes from papillary muscle and from epicardial tissue of adult and neonatal rabbits. The densities of the outward currents in neonatal cells were about one-half of the current density in adult cells. The density of the voltage-activated transient outward current (I(to1)) was smaller in cells from papillary muscle than in cells from epicardium in adult and newborn rabbits. We found major differences in the kinetic behavior of I(to1) between adult and neonatal cells: 1) the rate of apparent inactivation was faster in neonatal cells, and 2) the recovery from inactivation was significantly faster in neonatal cells, with a time constant of 113 vs. 1,356 ms. We propose that this marked difference in the recovery from inactivation of I(to1) is the basis for the difference in frequency dependence of action potential duration.

4-Aminopyridine↗
PubMed1994

Imipramine blocks rapidly activating and delays slowly activating K+ current activation in guinea pig ventricular myocytes.

Imipramine is a tricyclic antidepressant drug that also exhibits antiarrhythmic effects and whose clinical spectrum of activity is similar to that of quinidine. It has been previously demonstrated that imipramine inhibits the aggregate time-dependent outward K+ current (IK). IK is composed of at least two components: a slowly activating La(3+)-resistant delayed rectifying current (IK,s) and a rapidly activating La(3+)-sensitive current (IK,r). To assess the effects of imipramine on IK,r and IK,s, single guinea pig ventricular myocytes were studied using the nystatin-perforated patch-clamp technique in the absence and in the presence of La3+. Imipramine inhibited IK,r and IK,s in a concentration-dependent manner. The effects of imipramine on the aggregate time-dependent outward current were more marked than those on IK,s alone. Thus, 1 mumol/L imipramine decreased the tail currents elicited on return to -30 mV after long depolarizing pulses (5 seconds, from -40 to +50 mV) in the absence and in the presence of La3+ by 27 +/- 4% and 15 +/- 3% (n = 6), respectively. Moreover, the inhibition induced by imipramine was greater after short (0.5-second) pulses than after 5-second depolarizing pulses, both in the absence and in the presence of La3+ (53 +/- 3% and 30 +/- 5%, respectively; n = 6; P < .05). Imipramine did not significantly modify either the activation midpoint or the slope factor of the aggregate IK and IK,s activation curves. The reduction of IK,s by imipramine was voltage dependent and was more marked at negative membrane potentials. In the presence of 1 mumol/L imipramine, the ratio of tail current to time-dependent current remained constant at 0.37 +/- 0.03, regardless of the test pulse duration at +50 mV. Thus, the envelope-of-tails test was satisfied in the presence of 1 mumol/L imipramine, which indicates that imipramine, at this concentration, blocks IK,r. Imipramine (1, 5, and 10 mumol/L) had no effect on the kinetics of the later phase of IK activation but delayed the beginning of the activation of IK,s by 62 +/- 22, 74 +/- 23, and 155 +/- 53 milliseconds in the presence of 1, 5, and 10 mumol/L imipramine, respectively. These results suggest that imipramine preferentially blocks rapidly activating K+ channels. In addition, experiments performed in the presence of 30 mumol/L La3+ suggest that the drug preferentially binds, but maybe not exclusively, to a closed state of the slowly activating K+ channel.

Action Potentials↗
PubMed1992

Caffeine and theophylline contractures in tonic skeletal muscle fibers of the frog.

Caffeine and theophylline evoke maintained tension in tonic skeletal muscle fibers of the frog. Their effects depended upon concentrations ranging from 0.5 to 14 mM. The resting potential of tonic skeletal fiber was unaffected by caffeine or theophylline (4 mM). Caffeine and theophylline contractures have a peak tension followed by a sustained tension, which recovered spontaneously when returned to normal solution. The peak tension and total tension (the area under tension-time curve) were reduced when the fibers were soaked in calcium-free solution. In addition the tension was reduced by calcium channel blockers (cadmium). The sustained tension was increased when external calcium was raised. These results suggest that caffeine and theophylline promote the calcium release from sarcoplasmic reticulum and probably the entry of calcium from external medium.

Animals↗
PubMed1988

Effects of the novel antiarrhythmic compound TR 2985 (ropitoin) on action potentials of different mammalian cardiac tissues.

Ropitoin (TR 2985) is a novel antiarrhythmic drug. In the present work we have found that the main effect of the compound on the normal action potential of different cardiac tissues, guinea-pig atrial and ventricular muscle (1-3 mumol/l), and dog Purkinje fibres (0.5-1.0 mumol/l) was a depression of the maximum upstroke velocity. This effect was dependent on the frequency of stimulation, being stronger at higher frequencies. In the presence of the drug (3 mumol/l), we observed a shift of 9 mV of the resting membrane potential-maximum upstroke velocity relationship to more negative potentials. Under control conditions recovery from inactivation of maximum upstroke velocity was complete in less than 200 ms. Ropitoin induced a very slow component of recovery of the maximum upstroke velocity, explaining the frequency-dependent effects of the drug. The slow recovery of the maximum upstroke velocity induced by ropitoin was dependent on the membrane potential being faster at a more hyperpolarized membrane potential. The time course of the recovery was also dependent on pH; acidosis slowed it considerably. Ropitoin increased action potential duration of atrial muscle at 20% and 90% of repolarization. In contrast, the compound shortened action potential duration of ventricular muscle at 20% and 90% of repolarization, and dog Purkinje fibres at 50% and 90% of repolarization. In addition, ropitoin (1-3 mumol/l) depressed guinea-pig ventricular slow action potentials. This effect was the stronger the higher the stimulation frequency.

Action Potentials↗
PubMed1987

Characterization of the effects of histamine on the transmembrane electrical activity of guinea-pig and rabbit SA- and AV-node cells.

The effects of histamine on the transmembrane electrical activity of cells of small preparations (0.5 X 0.5 mm) of guinea-pig and rabbit sinoatrial- and atrioventricular-nodes were studied. Histamine at concentrations above 10(-7) mol/l increased the firing rate, the rate of diastolic depolarization, the maximum diastolic potential, the amplitude and the maximum rate of depolarization of the action potential of pacemaker cells of rabbit and guinea-pig sinoatrial cells and rabbit atrioventricular cells. These effects were antagonized by the H2-receptor blocker cimetidine (2.5 X 10(-6)mol/l) but they were not modified by the H1-receptor blocker chlorphenamine (2.5 and 5 X 10(-6)mol/l). Small preparations of guinea-pig atrioventricular node did not exhibit spontaneous activity, but it was induced by histamine and blocked by cimetidine. Histamine increased the maximum upstroke velocity of propagated action potential of cells of the central part of complete atrioventricular node in both species studied. These effects were blocked by cimetidine, but not by chlorphenamine. It is concluded that the increase in automaticity induced by histamine in guinea-pig and rabbit sinoatrial and atrioventricular nodes was due to stimulation of H2-receptors. Histamine did not depress electrical activity of atrioventricular node cells, but rather increased it. This effect was due to H2-receptor stimulation.

Action Potentials↗
PubMed1986

Further characterization of the receptors involved in the positive inotropic effect of histamine on rabbit papillary muscle.

The effects of histamine on the force of contraction and calcium-dependent action potentials were studied in rabbit ventricular papillary muscles. The positive inotropic effect of histamine seems to be dependent on stimulation of H1 and H2 receptors. The H1 antagonist chlorpheniramine produced a competitive blockade of the positive inotropic effects of histamine. Cimetidine produced a competitive blockade, which was apparent only after blockade of H1 receptors. Histamine increased the maximum upstroke velocity of slow action potentials. This effect can be entirely accounted for by stimulation of H2 receptors. The phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine potentiated the H2 receptor mediated effects of histamine on the force of contraction and slow action potentials. We conclude that rabbit ventricular muscle possesses both H1 and H2 receptors that mediate the positive inotropic effect of histamine. The H2-mediated effect seems to be causally related to an increase in the calcium slow inward current and is probably linked to an enhanced cellular cyclic adenosine monophosphate content. The mechanism of the H1-mediated positive inotropic effect remains unknown.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Selective reinnervation of twitch and tonic muscle fibres of the frog.

The electrical properties and innervation of piriformis muscle fibres and the conduction velocities and thresholds of the corresponding motor axons were studied. In normal muscles all fibres clearly fell into the category of twitch or tonic. Tonic muscle fibres were selectively reinnervated by small motor axons after crushing or cutting the piriformis nerve. Twitch fibres were reinnervated by large motor axons. Tonic fibres were also selectively reinnervated by small motor axons when the proximal stump of the piriformis nerve was cut and attached to the caudal end of the muscle. With this procedure the possibility of mechanical guidance by remaining neural sheaths was eliminated. Polyneuronal innervation in twitch fibres in piriformis muscles of normal frogs was 4.7% and in contralateral muscles of operated frogs with the piriformis nerve cut it was 22.6%. Unexpectedly three out of seventeen tonic fibres in contralateral muscles were simultaneously innervated by both small and large motor axons. It is concluded that reinnervation is highly specific for fibre type in frog skeletal muscles.

Animals↗
PubMed1979

Regional versus systemic heparinization.

In 12 mongrel dogs, the comparative effectiveness of systemic versus regional heparinization was studied after injecting 100 units per kilogram of heparin into a systemic vein or regionally into an artery. Activated plasma thromboplastin time was used to monitor the heparin activity, and the coagulability of blood in the general circulation was compared with the coagulability of blood in the excluded circulation distal to the vascular clamps. Both methods of heparinization were found to be equally effective. Heparin injected regionally rapidly achieves a uniform distribution in the excluded, as well as the general, circulation and, as such, cannot be called regional. There was no difference in coagulability of blood in the general circulation compared with the blood in the excluded circulation. Results of this study suggest that regional heparinization is, in fact, systemic heparinization.

Animals↗