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Biomedical subjects

A J Pappano

Publications and source records attributed to A J Pappano.

At least 73 records · Page 4Linked to original sources
PubMed1980

Muscarinic antagonism of the effects of phosphodiesterase inhibitor (methylisobutylxanthine) in embryonic chick ventricle.

Methylisobutylxanthine (MIX) augmented contractions and Ca++-dependent action potentials in ventricles isolated from embryonic and hatched chicks. Acetylcholine (ACh) inhibited these effects of MIX. In ventricles from chicks on the 18th incubation day, cyclic AMP content was increased to about 150% of basal after 3 min in 3 X 10(-4) M MIX. ACh (10(-6) M) did not reduce the cyclic AMP accumulation caused by MIX, although the increase in twitch tension was abolished. However, 10(-4) M ACh blocked the MIX-induced increases in both twitch tension and cyclic AMP. We conclude, therefore, that ACh antagonizes the effects of MIX both by blocking the action of elevated cyclic AMP and in higher concentrations, also by inhibiting the accumulation of cyclic AMP. In homogenates of chick ventricles. ACh neither stimulated phosphodiesterase activity nor blocked the inhibition of phosphodiesterase by MIX. Therefore, inhibition of cyclic AMP accumulation by higher concentrations of ACh may result from an inhibition of adenylate cyclase activity. Since neither 10(-6) nor 10(-4) M ACh reduced basal cyclic AMP content, basal adenylate cyclase is presumably not affected by ACh. We speculate that MIX may indirectly increase adenylate cyclase activity by antagonizing an inhibitory effect of endogenous adenosine. Furthermore, ACh may interfere with this effect of MIX, thereby facilitating the inhibition of adenylate cyclase by adenosine.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Epinephrine and the pacemaking mechanism at plateau potentials in sheep cardiac Purkinje fibers.

1. In 1.35 mM [K+]0, sheep cardiac Purkinje fibers depolarized to about -40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (-50 to 0 mV) was distinct from that caused by the iK2 pacemaker at more negative potentials (-60 to -100 mV). 2. Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5 x 10(-7) M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (isi, Reuter, 1974). 3. In voltage clamp experiments, epinephrine, increased the magnitude of isi and of an outward plateau current, ixi. It is concluded that epinephrine effects pacemaking at plateau potentials by increasing isi and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow through isi channels that are activated but not completely inactivated.

Animals↗
PubMed1979

Ontogenetic increase of the maximal rate of rise of the chick embryonic heart action potential. Relationship to voltage, time, and tetrodotoxin.

The maximal rate of rise (Vmax) of the embryonic chick ventricular action potential increased about 2-fold from 112 +/- 6 V/sec and 113 +/- 5 V/sec on the 4th and 6th incubation days, respectively, to 217 +/- 7 V/sec on the 12th incubation day. Neither the steady state inactivation (hinfinity) of Vmax, the temperature-dependent shift of hinfinity, nor the time constant for recovery (tauRec) of Vmax changed significantly when Vmax had doubled. Inhibition of Vmax by tetrodotoxin (TTX) was the same in hearts from the 4th, 6th, and 18th incubation days. The relation between Vmax and TTX concentration could be described by a one-to-one binding curve with an apparent dissociation constant of 2 X 10(-8) M. The increase of Vmax, a valid measure of the early inward Na+ current (iNa) during the rising phase of the cardiac action potential, can be attributed to an elevated maximal Na+ conductance (-gNa) during ontogenesis. These results indicate that the physicochemical properties of the gNa unit responsible for the rapid rising phase of the action potential and of the TTX binding site associated with it may remain constant during a period of embryonic development when -gNa increased significantly.

Action Potentials↗
PubMed1976

Action potentials in chick atria. Ontogenetic changes in the dependence of tetrodotoxin-resistant action potentials on calcium, strontium, barium.

Action potentials were recorded from chick embryo atrial muscle cells bathed in Tyrode's solution. Tetrodotoxin (TTX), 3.1 muM, was added to block the early, transient, Na+-dependent conductance system. Rectangular stimuli were used to evoke action potentials the peak amplitude (Ep) of which depend on the external concentration of divalent cations, [Me2+]0. The relationship between Ep and [Me2+]0 shifted to the right with increasing age. For example, the slope of Ep was 33 +/- 2,22 +/- 1 and 11 +/- 3 mV per 10-fold change in [Ca2+]0 on the 9th, 12th, and 18th incubation days, respectively. In solutions with reduced [Ca2+]0, Ep increased when Ba2+ or Sr2+ was added to the bath. The potency of Me2+ in generating action potentials was Ba2+ greater than Sr2+ greater than Ca2+ and this sequence did not change during development. Action potential amplitude, which was reduced in 18-day preparations, was increased by isoproterenol (increased Ca2+ conductance, gCa2+) and by tetraethylammonium (TEA) ion (decreased K+ conductance, gK). The results show that (1) Me2+-dependent action potentials support membrane excitation in chick atrial cells treated with TTX, and (2) the ability of Me2+ to support action potentials decreases during ontogenesis. We conclude from these experiments that the ontogenetically related decrease in Me2+-induced action potentials is the result of a reduction in gMe2+/gK+ during stimulation.

Action Potentials↗
PubMed1976

Mechanism for the postive inotropic effect of angiotensin II on isolated cardiac muscle.

Angiotensin II (A II) and analogues were tested for their ability to restore electrical and mechanical activity to cardiac muscle preparations in which the fast Na+ channels had been inactivated by partial depolarization (22-27 mM K+) or by tetrodotoxin (TTX). The partially depolarized or TTX-blocked preparations were chosen because under these conditions electrical and mechanical responses are primarily Ca2+ -dependent. In depolarized rabbit right atria, A II restored spontaneous mechanical and electrical activity (measured by both intracellular and extracellular recording techniques). The frequency of action potential discharge was concentration-dependent; the threshold concentration of A II was 10(-10) M, the ED50 was 8 X 10(-9) M, and the maximum effect was observed at 5 X 10(-8) M. In contrast, depolarized guinea pig atria were insensitive to A II, Sar1-angiotensin II, and des-Asp1-angiotensin II, even at concentrations as high as 10(-5) M. Rabbit papillary muscle (TTX-blocked), embryonic (18-day) chick heart (partially depolarized) and chick heart reaggregates (TTX-blocked) responded similarly to rabbit atria in that A II (9.6 X 10(-7) M) restored both electrical and mechanical activity. We found that in these preparations the action of A II was unaffected by propranolol (5.0 X 10(-6) M to 5.0 X 10(-5) M) but was blocked by Mn2+ (10(-3) M), D-600 (1 X 10(-7) g/ml) and the specific A II antagonists Sar1-Ala8-angiotensin II (P-113) (5.0 X 10(-5) M) and Sar1-Ile8-angiotensin II (5.28 X 10(-5) M). We conclude that the positive inotropic effect of A II on the myocardium is due to its ability to increase transmembrane ion movements in or through the cell membrane. The ability of Mn2+ and D-600 to block this effect suggests that this ion movement is via the so-called "slow channels."

Action Potentials↗
PubMed1976

Onset of chronotropic effects of nicotinic drugs and tyramine on the sinoatrial pacemaker in chick embryo heart: relationship to the development of autonomic neuroeffector transmission.

Spontaneous electrical activity, recorded extracellularly from the sinoatriial pacemaker region in the isolated chick embryo heart, was inhibited by nicotine (10(-5)M) on the 11th incubation day and thereafter. Blockade of the inhibitory effects of nicotine hexamethonium, tetroditoxin and atropine supported the conclusion that nicotine initiated propagated impulses in postganglionic cholinergic nerves and released acetylcholine to act on atropine-sensitive receptors on pacemaker cells. Dimethylphenylpiperazinium, like nicotine, inhibited the sinoatrial pacemaker. The onset of the inhibitory effect of nicotine occurred within 1 day of the appearance of cholinergic neuroeffector transmission. The acceleratory action of tyramine (2.9 X 10(-5)M) increased markedly on the 20th incubation day, that is, within 1 day of the appearance of adrenergic neuroeffector transmission. The positive chronotropic effects of tyramine were opposed by cocaine and by propranolol. Nicotine also evoked pacemaker acceleration that was observed on the 21st incubation day and thereafter. However, the sympathomimetic effect of nicotine required elevation (2 times normal) of the external Ca++ concentration. Ontogenetic and pharmacologic evidence support the conclusion that the drug-induced changes in pacemaker impulse frequency depended upon an interaction with autonomic nerves. The results are consistent with the hypothesis that the gap between morphologic innervation of the heart by autonomic nerves and the appearance of transmission is related, at least in part, to the amount of transmitter available for release.

Age Factors↗