Effects of antipsychotic drugs on action potential production in skeletal muscle. I. Chlorpromazine and promethazine

1977 ◽  
Vol 55 (3) ◽  
pp. 452-461 ◽  
Author(s):  
H. S. Buttar ◽  
G. B. Frank
Keyword(s):  
Action Potential ◽  
Muscle Fibers ◽  
Potassium Conductance ◽  
Input Resistance ◽  
Threshold Current ◽  
Resting Potential ◽  
Sartorius Muscle ◽  
Potential Production ◽  
Drug Concentrations ◽  
Local Anaesthetic Effect

The effects of chlorpromazine, an antipsychotic phenothiazine, and promethazine, an antihistaminic phenothiazine, on excitability and action potential production in frog's sartorius muscle fibers were studied and compared. Both drugs produced a local anaesthetic effect which developed slowly over 3 to 5 h with lower concentrations (1 to 15 × 10−6 M) and was only partially reversed by exposing the muscles to a drug-free solution for 3 to 4 h. The resting potential and the input resistance of the muscle fibers were unaffected by drug concentrations which reduced the action potential maximum rate of rise, the threshold current of 2-ms injected pulses and the intracellularly measured threshold depolarization. The effects on the action potential were antagonized in an apparently competitive manner by sodium ions. Thus both drugs depressed excitability and the rising phase of the action potential by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. It was shown that both drugs also inhibited the secondary rise in potassium conductance (gK) which normally occurs during an action potential. Although quantitatively similar, lower concentrations of chlorpromazine (> 15 × 10−6 M) were more potent and higher concentrations (> 15 × 10−6 M) were less potent than promethazine. The qualitatively identical and the quantitatively similar effects of these two drugs would suggest that the antipsychotic effect produced by some of the phenothiazines is unrelated to their effects on action potential production.

The interactive effects of fatigue and pH on the ionic conductance of frog sartorius muscle fibers

1985 ◽  
Vol 63 (11) ◽  
pp. 1444-1453 ◽  
Author(s):  
J. M. Renaud ◽  
G. W. Mainwood
Keyword(s):  
Action Potential ◽  
Normal Values ◽  
Muscle Fibers ◽  
Membrane Conductance ◽  
Interactive Effects ◽  
Resting Potential ◽  
Sartorius Muscle ◽  
Ionic Conductance ◽  
Frog Sartorius Muscle ◽  
Frog Sartorius

The effects of fatigue on the membrane conductance of frog sartorius muscle at the resting potential and during an action potential were studied. When muscles were exposed to an extracellular pH of 8.0 the membrane conductance at the resting potential increased during fatigue by about 20% and returned to prefatigue level in about 20 min. The membrane conductance of muscle fibers exposed to pH 6.4 was about three times less than that of pH 8.0 and decreased further during fatigue. Furthermore, the recovery of a normal membrane conductance was slow at pH 6.4. Both the inward, depolarizing and the outward, repolarizing currents during the action potential are reduced in fatigue. In each case the effect is greater at pH 6.4 than at 8.0 and recovery towards normal values is slower at pH 6.4. It is concluded that the ionic conductance of the sareolemmal membrane at the resting potential and during an action potential are modified by fatigue and that these changes are modulated by pHo.

Effects of K+ on the twitch and tetanic contraction in the sartorius muscle of the frog, Rana pipiens. Implication for fatigue in vivo

1992 ◽  
Vol 70 (9) ◽  
pp. 1236-1246 ◽  
Author(s):  
Jean Marc Renaud ◽  
Peter Light
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Muscle Fibers ◽  
Resting Potential ◽  
Sartorius Muscle ◽  
Coupling Mechanism ◽  
Tetanic Force ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
The Mean

The effects of increasing the extracellular K+ concentration on the capacity to generate action potentials and to contract were tested on unfatigued muscle fibers isolated from frog sartorius muscle. The goal of this study was to investigate further the role of K+ in muscle fatigue by testing whether an increased extracellular K+ concentration in unfatigued muscle fibers causes a decrease in force similar to the decrease observed during fatigue. Resting and action potentials were measured with conventional microelectrodes. Twitch and tetanic force was elicited by field stimulation. At pHo (extracellular pH) 7.8 and 3 mmol K+∙L−1 (control), the mean resting potential was −86.6 ± 1.7 mV (mean ± SEM) and the mean overshoot of the action potential was 5.6 ± 2.5 mV. An increased K+ concentration from 3 to 8.0 mmol∙L−1 depolarized the sarcolemma to −72.2 ± 1.4 mV, abolished the overshoot as the peak potential during an action potential was −12.0 ± 3.9 mV, potentiated the twitch force by 48.0 ± 5.7%, but did not affect the tetanic force (maximum force) and the ability to maintain a constant force during the plateau phase of a tetanus. An increase to 10 mmol K+∙L−1 depolarized the sarcolemma to −70.1 ± 1.7 mV and caused large decreases in twitch (31.6 ± 26.1%) and tetanic (74.6 ± 12.1%) force. Between 3 and 9 mmol K+∙L−1, the effects of K+ at pHo 7.2 (a pHo mimicking the change in interstitial pH during fatigue) and 6.4 (a pHo known to inhibit force recovery following fatigue) on resting and action potentials as well as on the twitch and tetanic force were similar to those at pHo 7.8. Above 9 mmol K+∙L−1 significant differences were found in the effect of K+ between pHo 7.8 and 7.2 or 6.4. In general, the decrease in peak action potential and twitch and tetanic force occurred at higher K+ concentrations as the pHo was more acidic. The results obtained in this study do not support the hypothesis that an accumulation of K+ at the surface of the sarcolemma is sufficiently large to suppress force development during fatigue. The possibility that the K+ concentration in the T tubules reaches the critical K+ concentration necessary to cause a failure of the excitation–contraction coupling mechanism is discussed.Key words: excitation–contraction coupling, fatigue, potassium, tetanus, twitch.

Effects of Morphine and Meperidine on Action Potential Production in Frog's Skeletal Muscle Fibers

1975 ◽  
Vol 53 (1) ◽  
pp. 92-96 ◽  
Author(s):  
G. B. Frank ◽  
H. S. Buttar
Keyword(s):  
Skeletal Muscle ◽  
Action Potential ◽  
Action Potential Duration ◽  
Muscle Fibers ◽  
Potassium Conductance ◽  
Potential Production ◽  
Skeletal Muscle Fibers ◽  
Adequate Stimulus ◽  
Specific Increase ◽  
Secondary Rise

Morphine (3.3 × 10−4–33 × 10−4 M) and meperidine (8.8 × 10−5–35 × 10−5 M) inhibited action potential production in frog's skeletal muscle fibers. Over these concentration ranges, neither the resting membrane potentials nor the resting membrane electric properties of the fibers appeared to be modified. Both drugs depressed excitability and the rising phase of the action potential by inhibiting the specific increase in sodium conductance which normally follows an adequate stimulus. Both drugs also seemed to inhibit the secondary rise in potassium conductance which normally occurs during an action potential, causing a prolongation of the action potential duration.

Effects of antipsychotic drugs on action potential production in skeletal muscle. II. Haloperidol: nonspecific and opiate drug receptor mediated effects

1977 ◽  
Vol 55 (3) ◽  
pp. 462-470 ◽  
Author(s):  
H. D. Durham ◽  
G. B. Frank ◽  
J. Marwaha
Keyword(s):  
Action Potential ◽  
Potassium Conductance ◽  
Sartorius Muscle ◽  
Potential Production ◽  
Mediated Effects ◽  
Low Concentrations ◽  
Adequate Stimulus ◽  
Intracellular Microelectrodes ◽  
Drug Receptor ◽  
Opiate Drug

The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anaestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 × 10−6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 × 10−8 and 2.8 × 10−7 M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa.

Posttetanic hyperpolarization produced by electrogenic Na(+)-K+ pump in lizard axons impaled near their motor terminals

1993 ◽  
Vol 70 (5) ◽  
pp. 1874-1884 ◽  
Author(s):  
K. Morita ◽  
G. David ◽  
J. N. Barrett ◽  
E. F. Barrett
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Input Resistance ◽  
Peak Amplitude ◽  
Resting Potential ◽  
Tetanic Stimulation ◽  
Train Duration ◽  
Consistent Change ◽  
Nodal Voltage

1. The hyperpolarization that follows tetanic stimulation was recorded intra-axonally from the internodal region of intramuscular myelinated motor axons. 2. The peak amplitude of the posttetanic hyperpolarization (PTH) that followed stimulation at 20-100 Hz for < or = 35 s increased with increasing train duration, reaching a maximum of 22 mV. PTH decayed over a time course that increased from tens to hundreds of seconds with increasing train duration. For a given frequency of stimulation the time integral of PTH was proportional to the number of stimuli in the train, averaging 3-4 mV.s per action potential. 3. Ouabain (0.1-1 mM) and cyanide (1 mM) depolarized the resting potential and abolished PTH. Tetanic stimulation in ouabain was followed by a slowly decaying depolarization (probably due to extra-axonal K+ accumulation) whose magnitude and duration increased as the duration of the train increased. 4. Axonal input resistance showed no consistent change during PTH in normal solution but increased during PTH in the presence of 3 mM Cs+ (which blocks axonal inward rectifier currents). 5. PTH was abolished when bath Na+ was replaced by Li+ or choline. PTH persisted after removal of bath Ca2+ and addition of 2 mM Mn2+. 6. Removal of bath K+ abolished the PTH recorded after brief stimulus trains and greatly reduced the duration of PTH recorded after longer stimulus trains. 7. A brief application of 10 mM K+, which normally depolarizes axons, produced a ouabain-sensitive hyperpolarization in axons bathed in K(+)-free solution. 8. These observations suggest that in these myelinated axons PTH is produced mainly by activation of an electrogenic Na(+)-K(+)-ATPase, rather than by changes in K+ permeability or transmembrane [K+] gradients. This conclusion is supported by calculations showing agreement between estimates of Na+ efflux/impulse based on PTH measurements and estimates of Na+ influx/impulse based on nodal voltage-clamp measurements. Pump activity also appears to contribute to the resting potential. 9. The stimulus intensity required to initiate a propagating action potential increased during PTH but decreased during the posttetanic depolarization recorded in ouabain. Thus changes in axonal excitability after tetanic stimulation correlate with changes in the posttetanic membrane potential. 10. Action potentials that propagated during PTH had a larger peak amplitude and were followed by a larger and longer depolarizing afterpotential than action potentials elicited at the resting potential. This enhancement of the depolarizing afterpotential is consistent with previous reports of an increased superexcitable period after action potentials evoked during PTH.

scholarly journals Tetrodotoxin Blockage of Sodium Conductance Increase in Lobster Giant Axons

1964 ◽  
Vol 47 (5) ◽  
pp. 965-974 ◽  
Author(s):  
Toshio Narahashi ◽  
John W. Moore ◽  
William R. Scott
Keyword(s):  
Action Potential ◽  
Potassium Conductance ◽  
Complete Recovery ◽  
Selective Inhibition ◽  
Resting Potential ◽  
Normal Medium ◽  
Giant Axons ◽  
Sodium Conductance ◽  
Puffer Fish ◽  
Conductance Increase

Previous studies suggested that tetrodotoxin, a poison from the puffer fish, blocks conduction of nerve and muscle through its rather selective inhibition of the sodium-carrying mechanism. In order to verify this hypothesis, observations have been made of sodium and potassium currents in the lobster giant axons treated with tetrodotoxin by means of the sucrose-gap voltage-clamp technique. Tetrodotoxin at concentrations of 1 x 10-7 to 5 x 10-9 gm/ml blocked the action potential but had no effect on the resting potential. Partial or complete recovery might have occurred on washing with normal medium. The increase in sodium conductance normally occurring upon depolarization was very effectively suppressed when the action potential was blocked after tetrodotoxin, while the delayed increase in potassium conductance underwent no change. It is concluded that tetrodotoxin, at very low concentrations, blocks the action potential production through its selective inhibition of the sodium-carrying mechanism while keeping the potassium-carrying mechanism intact.

scholarly journals On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart.

1978 ◽  
Vol 71 (1) ◽  
pp. 47-67 ◽  
Author(s):  
D J Miller ◽  
A Mörchen
Keyword(s):  
Ethylene Glycol ◽  
Action Potential ◽  
Calcium Ions ◽  
Action Potentials ◽  
Time Course ◽  
Divalent Cations ◽  
Potassium Conductance ◽  
Resting Potential ◽  
Slow Inward Current ◽  
Frog Heart

Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively "leaky" in EGTA solutions.

Electrical properties of oxytocin neurons in organotypic cultures from postnatal rat hypothalamus

1996 ◽  
Vol 76 (4) ◽  
pp. 2772-2785 ◽  
Author(s):  
P. Jourdain ◽  
D. A. Poulain ◽  
D. T. Theodosis ◽  
J. M. Israel
Keyword(s):  
Electrical Properties ◽  
Action Potential ◽  
Glutamate Receptors ◽  
Action Potentials ◽  
Firing Pattern ◽  
Membrane Conductance ◽  
Input Resistance ◽  
Resting Potential ◽  
Organotypic Cultures ◽  
Current Pulses

1. Intracellular recordings were performed on immunocytochemically identified oxytocin (OT) neurons (n = 101) maintained for 2-7 wk in hypothalamic organotypic cultures derived from 4-to 6-day-old rat neonates. The neurons displayed a resting potential of -58.9 +/- 6.8 mV (mean +/- SD, n = 74), an input resistance of 114 +/- 26.8 M omega (n = 66), and a time constant of 9.6 +/- 1.4 ms (n = 57). Voltage-current (V-I) relations, linear at resting potential, showed a pronounced outward rectification when depolarized from hyperpolarized membrane potentials. At these hyperpolarized potentials, depolarizing current pulses induced a delayed action potential. 2. Action potentials had an amplitude of 73.4 +/- 9.7 mV and a duration of 1.9 +/- 0.2 ms. Each action potential was followed by an afterhyperpolarization of 7.9 +/- 2.0 mV in amplitude lasting 61.7 +/- 11.3 ms. The depolarizing phase of action potentials was both Na+ and Ca2+ dependent, whereas repolarization was due to a K+ conductance increase. 3. When Ba2+ was substituted for Ca2+ in the medium, OT neurons displayed prolonged sustained depolarizations. In the presence of tetrodotoxin (TTX), these depolarizations were triggered by depolarizing current pulses and arrested by hyperpolarizing current pulses or by local application of Ca2+, Co2+, Cd2+, No sustained depolarization was obtained when nifedipine was added to the medium. These data suggest that OT cells in organotypic culture possess L-type Ca2+ channels. 4. All OT neurons generated spontaneous action potentials at resting potential. Of 59 neurons, 29 showed a slow, irregular firing pattern (< or = 2.5 spikes/s), 24 generated a fast continuous firing pattern (> or = 2.5 spikes/s), and 6 cells displayed a bursting pattern of activity consisting of alternating periods of spike discharge and quiescence. None of the bursting cells exhibited regenerative endogenous potentials (plateau potentials). On the contrary, in four of these cells, the bursting activity was clearly due to patterned synaptic activity. 5. The cultured OT cells responded to exogenous gamma-aminobutyric acid (GABA) and muscimol with a hyperpolarization and an increase in membrane conductance. These effects still were observed in the presence of TTX, indicating that they were due to direct activation of GABA receptors in the cells. The GABA-induced response was mediated by GABAA receptors because it was blocked by bicuculline, but not by GABAB receptors, because baclofen and hydroxysaclofen had no effect on membrane potential and input resistance. 6. OT neurons responded to exogenous glutamate, quisqualate, and kainate with a depolarization concomitant with an increase in membrane conductance. N-methyl-D-aspartate depolarized the cells in Mg(2+)-free medium. These effects were observed in the presence of TTX, suggesting that OT cells expressed ionotropic glutamate receptors. Trans-(1S,3R)-1-amino-1,3-cyclopentane-dicarboxylic acid and (+/-)-alpha-amino-4-carboxymethylphenylglycine had no effect on OT cells, thus excluding the presence of metabotropic glutamate receptors. 7. Taken together, our observations demonstrate that hypothalamic slice cultures from 4- to 6-day-old rat neonates contain well-differentiated OT neurons that display electrical properties similar to those shown by adult neurons in vitro. Such cultures provide a reliable model to investigate membrane properties of adult OT neurons and a useful means to study the long-term modulation of their electrical behaviour by various agents known to affect OT cells in vivo.

Effect of dinitrophenol on phosphorylation and bioelectric phenomena of excitable tissues

1961 ◽  
Vol 200 (3) ◽  
pp. 431-436 ◽  
Author(s):  
L. G. Abood ◽  
K. Koketsu ◽  
K. Noda
Keyword(s):  
Energy Metabolism ◽  
Muscle Fibers ◽  
Resting Potential ◽  
Sartorius Muscle ◽  
Nerve Roots ◽  
Intracellular Potassium ◽  
Frog Sartorius Muscle ◽  
Anodal Polarization ◽  
Frog Sartorius

The effect of 2, 4-dinitrophenol (DNP) was investigated on the phosphorylation of frog sartorius muscle and ventral nerve roots, using P32 as a tracer. It was possible almost completely to inhibit phosphorylation without significantly altering excitability, although the resting potential and intracellular potassium decreased over 30%. The addition of 0.01 mm DNP to a sodium-free hydrazinium system completely blocked excitability, despite the fact that this concentration of DNP produced no further inhibition of phosphorylation. It was possible to restore the excitability of frog sartorius muscle fibers by anodal polarization after the fibers were rendered inexcitable by immersion in 1 mm DNP. The results were discussed in terms of the role of energy metabolism in excitability and other bioelectric phenomena of muscle and nerve.

scholarly journals Ionic Conductances of the Surface and Transverse Tubular Membranes of Frog Sartorius Fibers

1969 ◽  
Vol 53 (3) ◽  
pp. 279-297 ◽  
Author(s):  
Robert S. Eisenberg ◽  
Peter W. Gage
Keyword(s):  
Statistical Analysis ◽  
Potassium Conductance ◽  
Input Resistance ◽  
Low Ph ◽  
Chloride Conductance ◽  
Membrane Properties ◽  
Sartorius Muscle ◽  
Ionic Conductances ◽  
Tubular Membranes ◽  
Frog Sartorius

The resting ionic conductances of frog sartorius muscle fibers have been determined in a variety of conditions in order to measure the potassium conductance of the tubular and surface membranes (gKt and gKs) and the chloride conductance of the tubular and surface membranes (gClt and gCls). In both normal fibers and fibers without tubules, measurements of input resistance and diameter were made at normal pH and at low pH when the chloride conductance was very small. These measurements permitted the separation of the ionic conductances: gCls = 219 µmhos/cm2; gClt = 0 µmhos/cm2; gKs = 28 µmhos/cm2; gKt = 55 µmhos/cm2. Possible sources of systematic error are discussed and a statistical analysis of the effects of random error is presented. The implications of the nonuniformity of membrane properties are discussed along with possible anatomical explanations.

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