Calcium antagonist blockade of slow action potentials in cultured chick heart cells

1983 ◽  
Vol 61 (9) ◽  
pp. 957-966 ◽  
Author(s):  
Tung Li ◽  
Nick Sperelakis
Keyword(s):  
Action Potentials ◽  
Rest Period ◽  
Independent Effect ◽  
Heart Cells ◽  
Maximal Effect ◽  
Response Curves ◽  
Dependent Component ◽  
Chick Heart ◽  
Kinetics Of ◽  
Slow Action Potentials

The effects of four Ca antagonists, bepridil, diltiazem, nifedipine, and verapamil, on slow channels were studied in cultured cell reaggregates prepared from 14-day-old chick embryonic, hearts. The cell membrane was partially depolarized to about −45 mV by using 22 mM KCl to inactivate the fast Na+ channels. Slow action potentials were induced by 10−6 M isoproterenol with electrical stimulation. Cumulative dose – response curves for the effect of the four drugs on the blocking of slow action potentials (using [Formula: see text] as the indicator) were analyzed by Hill plots. The dose values for 50% of maximal effect, at a stimulation frequency of 60/min, were (in order of decreasing potencies) as follows: 5.2 × 10−9 M for nifedipine, 3.1 × 10−7 M for diltiazem, 1.2 × 10−6 M for verapamil, and 5.1 × 10−6 M for bepridil. The effect of all four Ca antagonists showed use (or frequency)-dependency, i.e., the drugs were more effective at higher stimulation rates. This may reflect a blocking action of the drugs on the nonresting states of the channels and (or) a slowing of the recovery kinetics of the channels from the inactivated state back to the resting state. In a separate type of experiment utilizing a 5-min rest period in the presence of the drugs, nifedipine blocked and bepridil exhibited some depression of the first action potential elicited, i.e., use-independent effect, indicating that these drugs may also act on resting channels. Thus, these four Ca antagonists have a prominent use-dependent component in their actions, and one or two may also have a use-independent component.

Injection of guanosine 5'-cyclic monophosphate into heart cells blocks calcium slow channels

1985 ◽  
Vol 248 (5) ◽  
pp. H745-H749 ◽  
Author(s):  
G. Bkaily ◽  
N. Sperelakis
Keyword(s):  
Cyclic Nucleotides ◽  
Action Potentials ◽  
Heart Cells ◽  
Myocardial Cells ◽  
Cyclic Monophosphate ◽  
Intracellular Injection ◽  
Ventricular Cells ◽  
Camp And Cgmp ◽  
Slow Action Potentials

The role of guanosine 5'-cyclic monophosphate (cGMP) in the regulation of the ionic slow channels in heart muscle is less well known than that of adenosine 3,'5'-cyclic monophosphate (cAMP). The effects of intracellular injection of cAMP and cGMP in cultured chick embryonic heart (ventricular) cells by the liposome method were studied. Injection of cAMP into the cells induced spontaneous slow action potentials that could be blocked by verapamil and nifedipine. Injection of cGMP blocked on-going slow action potentials, and this effect was reversed by increasing cAMP. Thus both cAMP and cGMP are involved in the regulation of the slow calcium channels in myocardial cells, and the two cyclic nucleotides are antagonistic.

Insensitivity of cultured chick heart cells to autonomic agents and tetrodotoxin

1965 ◽  
Vol 209 (4) ◽  
pp. 693-698 ◽  
Author(s):  
Nick Sperelakis ◽  
D. Lehmkuhl
Keyword(s):  
Action Potentials ◽  
Bridge Circuit ◽  
Single Cells ◽  
Heart Cells ◽  
Culture Dish ◽  
Chemical Agents ◽  
Ventricular Cells ◽  
Pacemaker Potentials ◽  
Chick Heart ◽  
Frequency Of Action Potentials

Trypsin-dispersed cells from heart (ventricles) of 7- to 8-day chick embryos and 6-day posthatched chicks were cultured 2–15 days. The isolated single cells became attached to the bottom of the culture dish and reassembled into various monolayer communities; the cells of one community usually contracted synchronously. By means of a bridge circuit, one microelectrode was used for simultaneously passing current and recording membrane potentials. The following chemical agents were electrophysiologically inactive at or below the concentrations indicated (in g/ml): acetylcholine (1.1 x 10–4), epinephrine (2 x 10–4), norepinephrine (3 x 10–4), and tetrodotoxin (1.3 x 10–5). In contrast, 2–7 mm Ba++ (used as a control) was very effective in partially depolarizing the cells, initiating spontaneity, and increasing the frequency of action potentials. Thus, cultured chick ventricular cells, both pacemaker and nonpacemaker, are insensitive to the autonomic agents. The data also suggest that acetylcholine is not necessarily involved in the electrogenesis of pacemaker potentials. The lack of effect of tetrodotoxin is unexplained.

Effects of taurine on the electrical and mechanical activities of embryonic chick heart

1986 ◽  
Vol 64 (5) ◽  
pp. 649-655 ◽  
Author(s):  
Akihiko Sawamura ◽  
Nick Sperelakis ◽  
Junichi Azuma ◽  
Susumu Kishimoto
Keyword(s):  
Action Potentials ◽  
Cultured Cells ◽  
Negative Inotropic Effect ◽  
Embryonic Chick ◽  
Inotropic Action ◽  
Positive Inotropic Action ◽  
Chick Heart ◽  
Embryonic Chick Heart ◽  
Electrical And Mechanical Activities ◽  
Slow Action Potentials

The effect of taurine (2-aminoethanesulphonic acid) on myocardial slow action potentials (APs) and accompanying contractions was examined in isolated perfused chick hearts and reaggregated cultured cells. Isoproterenol (ISO), histamine (HIS), or tetraethylammonium (TEA) induced slow APs and contractions in hearts whose fast Na+ channels had been inactivated by elevated K+. Taurine (10 mM) not only failed to induce slow APs, but actually decreased ISO (10−8 M), HIS (10−4 M), or TEA (10 mM) induced slow APs and contractions transiently (about 30s –2 min after the addition of taurine). The properties of the slow APs recovered to control levels by 7–13 min after the addition of the taurine; at this time, there was an increase in developed tension of the contraction accompanying the slow APs. These results suggest that the positive inotropic action of taurine is not mediated through an increase in the slow inward Ca2+ current. However, the transient depression of Ca2+-dependent slow APs by taurine probably explains the transient negative inotropic effect of taurine.

Age-dependent changes in electrophysiologic characteristics of fast and slow action potentials in rat papillary muscle

1983 ◽  
Vol 61 (12) ◽  
pp. 1509-1515 ◽  
Author(s):  
Michio Kojima ◽  
Nick Sperelakis ◽  
Gordon Johnson ◽  
Stewart Ehrreich ◽  
Tibor Balazs
Keyword(s):  
Young Adult ◽  
Dose Response ◽  
Action Potentials ◽  
Resting Potential ◽  
Average Weight ◽  
Response Curves ◽  
Adult Rats ◽  
Age Dependent ◽  
Β Adrenergic Receptors ◽  
Slow Action Potentials

Isolated papillary muscles from juvenile (about 2 months old, average weight of 250 g) and young adult rats (about 4 months old, average weight 485 g) were studied for age-dependent differences in the characteristics of fast and slow action potentials (APs). The fast and slow APs were recorded in 5.4 mM and 25 mM K+-Tyrode solutions, respectively (stimulation rate of 1 Hz). For the slow APs, the dose–response curves for isoproterenol versus [Formula: see text] (the maximum rate of rise of the APs), overshoot, and AP amplitude were linear between 10−9 M and 10−6 M (10−5 M in some cases) in the juvenile and young adult rats. Isoproterenol pretreatment (1 mg/kg s.c, 1 h prior) decreased the slope of the dose–response curve, and saturation was achieved at a lower concentration. The [Formula: see text], overshoot, and amplitude of both the fast and slow APs were somewhat smaller in the young adult rats than in the juvenile rats; there were no differences in the resting potential, AP duration, or threshold voltage. These results suggest that activation of a greater fraction of the β-adrenergic receptors is coupled directly or indirectly to activation of a greater fraction of the slow channels. The pretreatment data suggest that down-regulation of the β-adrenergic receptor may occur. The conductance per channel for the fast Na+ channels and slow channels, and (or) the number of both types of functional channels, may decrease with age.

Injection of protein kinase inhibitor into cultured heart cells blocks calcium slow channels

1984 ◽  
Vol 246 (4) ◽  
pp. H630-H634 ◽  
Author(s):  
G. Bkaily ◽  
N. Sperelakis
Keyword(s):  
Protein Kinase ◽  
Action Potentials ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Heart Cells ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Cultured Heart Cells ◽  
Slow Action Potentials

An inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase was injected into cultured heart cells (reaggregates) by the phosphatidylcholine liposome method. The inhibitor blocked both the isoproterenol-induced slow action potentials and the spontaneously occurring slow action potentials of these cells. The inhibitory effect of protein kinase inhibitor was prevented by denaturation or reversed by the injection of the catalytic subunit of cAMP-dependent protein kinase. These findings support the phosphorylation hypothesis for the myocardial slow channels, namely that the slow channel protein must be phosphorylated for the channel to be available for voltage activation.

scholarly journals Ionic Interconversion of Pacemaker and Nonpacemaker Cultured Chick Heart Cells

1966 ◽  
Vol 49 (5) ◽  
pp. 867-895 ◽  
Author(s):  
Nick Sperelakis ◽  
D. Lehmkuhl
Keyword(s):  
Action Potentials ◽  
Bridge Circuit ◽  
Input Resistance ◽  
Membrane Potentials ◽  
Heart Cells ◽  
Chick Embryos ◽  
Pacemaker Cells ◽  
Culture Dish ◽  
A Cell ◽  
Chick Heart

Trypsin-dispersed cells from hearts (ventricles) of 7 to 8 day chick embryos were cultured 3 to 21 days. The cells became attached to the culture dish and assembled into monolayer communities. By means of a bridge circuit, one microelectrode was used for simultaneously passing current and recording membrane potentials (Vm). The input resistance, calculated by the measured ΔVm for a known step of current, averaged 10 MΩ. Electrotonic depolarization of nonpacemaker cells had no effect on frequency of firing. Within 2 min after addition of Ba++ (5 to 10 mM) to the Tyrode bath, the cells became partially depolarized and quiescent nonpacemaker cells developed oscillations in Vm which led to action potentials. With time, the depolarization became nearly complete and the input resistance increased 2 to 10 times. During such sustained depolarizations, action potentials were no longer produced and often tiny oscillations were observed; however, large action potentials developed during hyperpolarizing pulses. Thus, the automaticity of the depolarized cell became apparent during artificial repolarization. Sr++ (5 to 10 mM) initially produced hyperpolarization and induced automaticity in quiescent nonpacemaker cells. Elevated [K+]o (20 to 30 mM) suppressed automaticity of pacemaker cells and decreased Rm concomitantly. Thus, Ba++ probably converts nonpacemaker cells into pacemaker cells independently of its depolarizing action. Ba++ may induce automaticity and depolarization by decreasing gK, and elevated [K+]o may depress automaticity by increasing gK. The data support the hypothesis that the level of gK determines whether a cell shall function as a pacemaker.

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