Reduction in transmembrane Ca influx induced by the negative inotropic action of nicardipine in frog ventricular muscle

1986 ◽  
Vol 64 (7) ◽  
pp. 927-930
Author(s):  
Junna Hatae

The effects of nicardipine, a new 1,4-dihydropyridine derivative, on electrical and mechanical properties of frog ventricular muscle were examined. Nicardipine (3 × 10−7 M) reduced the twitch tension, and this reduction was frequency dependent, and considerable, in case of high frequencies. The resting potential was not affected by nicardipine (3 × 10−7 M), but the plateau height of the action potential was decreased and the duration of the action potential was shortened. The suppression of this plateau height was frequency dependent. The nicardipine-induced suppression of tension and action potential could be almost completely antagonized by raising the concentration of [Ca]o or by applying isoprenaline (8 × 10−7 M). These results suggest that the negative inotropic action of nicardipine is induced mainly by a reduction in the transmembrane Ca influx.

1964 ◽  
Vol 206 (5) ◽  
pp. 975-979 ◽  
Author(s):  
Morris Kleinfeld ◽  
Edward Stein ◽  
Bernard Murphy

Parachloromercuribenzoate (0.5 to 2.6 x 10–4 m) was administered to a hog Purkinje fiber ventricular muscle preparation and its effects on transmembrane action potentials of the two types of fibers were studied. Parachloromercuribenzoate produced changes in action potential of Purkinje but little change in that of ventricular fiber. The earliest alteration in Purkinje fiber was a decrease in overshoot. This was followed by a decrease in height of action potential and slowing in rate of depolarization. There was a decline in diastolic resting potential but this occurred late. The difference in response of the two types of fibers is not readily explainable. One possible difference is that the sulfhydryl groups in Purkinje fiber may be more available for binding with p-chloromercuribenzoate. Another hypothesis is predicated on differences in metabolism in two types of fibers. There is evidence to indicate that Purkinje fiber utilizes anaerobic glycolysis predominantly. A greater sensitivity of the glycolytic-dependent sulfhydryl enzymes to action of this agent would interfere with metabolism in Purkinje fiber and cause a decrease in its resting potential.


1979 ◽  
Vol 236 (2) ◽  
pp. H356-H370 ◽  
Author(s):  
J. J. Fenoglio ◽  
H. S. Karagueuzian ◽  
P. L. Friedman ◽  
A. Albala ◽  
A. L. Wit

Transmembrane potentials and ultrastructure of subendocardial Purkinje and ventricular muscle fibers, isolated 1, 3, 5, 6, 14, and 24 h after coronary occlusion were investigated. Action potentials were recorded from progressively fewer layers of muscle cells as the age of the infarct increased. At 14 h little viable muscle remained. The decrease in the number of electrophysiologically viable muscle fibers correlated with structural evidence that the infarct moved with time toward the endocardial surface until only viable Purkinje fibers remained. Purkinje and surviving ventricular muscle fibers demonstrated a progressive decrease in resting potential, action potential amplitude, and Vmax and a progressive increase in action potential duration. Spontaneous diastolic depolarizations were found in Purkinje fibers only in 24-h infarcts and occasionally in cells deep to the endocardial surface, which may have been muscle cells. We hypothesize that during the first 24 h after coronary occlusion arrhythmias originate near the interface of infarcted and ischemic myocardium. As this interface moves toward the endocardium, this site of origin of arrhythmias moves with it until the Purkinje network is reached.


2000 ◽  
Vol 41 (4) ◽  
pp. 481-492
Author(s):  
Naohiko Takahashi ◽  
Morio Ito ◽  
Shuji Ishida ◽  
Takao Fujino ◽  
Mikiko Nakagawa ◽  
...  

1972 ◽  
Vol 57 (2) ◽  
pp. 551-567
Author(s):  
T. YAMAMOTO

1. Electrical and mechanical properties of the red muscle (M. levator pinnae pectoralis) and white muscle (M. levator pinnae lateralis abdominis) in the silver carp (Carassius auratus Linné) were investigated by using caffeine and thymol. 2. A complete tetanus could be produced in the red muscle. But in the white muscle no tetanus was produced and there was a gradual decrease in tension during continuous stimulation, even at a frequency of 1 c/s or less. 3. Caffeine (0.5-1 mM) and thymol (0.25-0.5 mM) potentiated the twitch tension in both muscles without an increase in the resting tension; they produced a contracture in both muscles when the concentration was increased further. 4. The falling phase of the active state of contraction was nearly the same in both muscles and was prolonged by caffeine (0.5 mmM) and by thymol (0.25 mM). 5. The resting membrane potential of the red muscle was scarcely affected by caffeine (0.5-5 mM), whereas in the white muscles a depolarization of 10 mV was observed with caffeine of more than 2 mM. The resting potential of both muscles was little changed by o.25 mm thymol. However, at a concentration of more than 0.5mM thymol depolarized the membrane in both muscles to the same extent. 6. In caffeine (2-3 mM) solution the mean specific membrane resistance was reduced from 8.8 kΩ cm2 to 6.0 kΩ cm2 in the red muscle, and from 5.0 kΩ cm2 to 2.7 kΩ cm2 in the white muscle. In thymol (0.5-1 mM) solution it was reduced from 11.2 kΩcm2 to 6.5 kΩ cm2 in the red muscle, and from 5.4kΩ cm2 to 3.1 kΩ) cm2 in the white muscle. The specific membrane capacitance, calculated from the time constant and the membrane resistance, remained more or less the same in both muscles after a treatment with these agents. 7. Electrical properties of the muscles and the effects of caffeine and thymol on mechanical responses suggest that there are no fundamental differences between red and white muscles except for the excitation-contraction coupling. A lack of summation of twitch, a successive decline of twitch, and inability to produce potassium contracture in the white muscle may be due to the fact that the Ca-releasing mechanism is easily inactivated by depolarization of the membrane.


1974 ◽  
Vol 60 (3) ◽  
pp. 653-671
Author(s):  
D. B. SATTELLE

1. A mean resting potential of -53.3 (S.D. ±2.7) mV has been obtained for 23 neurones of the parietal and visceral ganglia of Limnaea stagnalis (L.). Changes in the resting potential of between 28 and 43 mV accompany tenfold changes in [K+0]. A modified constant-field equation accounts for the behaviour of most cells over the range of external potassium concentrations from 0-5 to 10.o mM/1. Mean values have been estimated for [K+1, 56.2 (S.D.± 9-0) mM/1 and PNa/PK, 0-117 (S.D.±0-028). 2. Investigations on the ionic basis of action potential generation have revealed two cell types which can be distinguished according to the behaviour of their action potentials in sodium-free Ringer. Sodium-sensitive cells are unable to support action potentials for more than 8-10 min in the absence of sodium. Sodium slopes of between 29 and 37 mV per decade change in [Na+0] have been found for these cells. Tetrodotoxin (5 x 10-5 M) usually blocks action potentials in these neurones. Calcium-free inger produces a marked reduction in the overshoot potential and calcium slopes of about 18 mV per decade change in [Ca2+o] are found. Manganous chloride only partially reduces the action potential overshoot in these cells at concentrations of 10 mM/l. 3. Sodium-insensitive neurones maintain action potentials in the absence of external sodium. Stimulation only slightly reduces the amplitude of the action potential under these conditions and such cells are readily accessible to potassium ions in the bathing medium. A calcium-slope of 29 mV per decade change in [Ca2+o] has been observed in these cells in the absence of external sodium. 4. It is concluded that both sodium and calcium ions can be involved in the generation of the action potential in neurones of Limnaea stagnate, their relative contribution varying in different cells.


2018 ◽  
Vol 124 (20) ◽  
pp. 205104 ◽  
Author(s):  
Mykola Lugovy ◽  
Amjad Aman ◽  
Nina Orlovskaya ◽  
Viktor Slyunyayev ◽  
Thomas Graule ◽  
...  

1991 ◽  
Vol 65 (5) ◽  
pp. 1055-1066 ◽  
Author(s):  
B. A. Ballyk ◽  
S. J. Quackenbush ◽  
R. D. Andrew

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)


2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.


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