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.

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.

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.

An investigation of the activity of opiate drug receptors located on frog skeletal muscle fibre membrane

1978 ◽  
Vol 56 (3) ◽  
pp. 501-508 ◽  
Author(s):  
G. B. Frank ◽  
J. Marwaha
Keyword(s):  
Skeletal Muscle ◽  
Action Potentials ◽  
Skeletal Muscle Fibre ◽  
Second Phase ◽  
Frog Skeletal Muscle ◽  
Potential Production ◽  
Low Concentrations ◽  
Drug Receptors ◽  
Frog Sartorius ◽  
Opiate Drug

Extracellular and intracellular microelcctrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors.

ACTION OF ETHER ON FROG SKELETAL MUSCLE

1965 ◽  
Vol 43 (5) ◽  
pp. 751-761 ◽  
Author(s):  
F. Inoue ◽  
G. B. Frank
Keyword(s):  
Skeletal Muscle ◽  
Action Potential ◽  
Electrical Activity ◽  
Effective Resistance ◽  
Frog Skeletal Muscle ◽  
Sodium Conductance ◽  
Low Concentrations ◽  
Adequate Stimulus ◽  
Specific Increase ◽  
Microelectrode Techniques

The mechanisms for the excitability changes produced by ether on the electrical activity of frog skeletal muscle were investigated by intracellular microelectrode techniques. Low concentrations of ether (less than 1%) increased excitability by increasing the 'effective resistance' between the inside and the outside of the fiber at the point of stimulation, thereby reducing the current needed to initiate an action potential. Higher concentrations decreased excitability by inhibiting the specific increase in sodium conductance which normally follows an adequate stimulus and is responsible for the rising phase of the action potential.

scholarly journals Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

2002 ◽  
Vol 136 (4) ◽  
pp. 540-549 ◽  
Author(s):  
Andrea Olschewski ◽  
Matthias Wolff ◽  
Michael E Bräu ◽  
Gunter Hempelmann ◽  
Werner Vogel ◽  
...  
Keyword(s):  
Potassium Conductance ◽  
Local Anaesthetics ◽  
Delayed Rectifier ◽  
Sensory Neurones ◽  
Low Concentrations

Dendrotoxin blocks accommodation in frog myelinated axons

1989 ◽  
Vol 62 (1) ◽  
pp. 174-184 ◽  
Author(s):  
M. O. Poulter ◽  
T. Hashiguchi ◽  
A. L. Padjen
Keyword(s):  
Action Potential ◽  
Computer Model ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Constant Stimulus ◽  
Motor Axons ◽  
Myelinated Axons ◽  
Frequency Adaptation ◽  
Potassium Conductances ◽  
Slow Potassium

1. Intracellular microelectrode recordings from large sensory and motor myelinated axons in spinal roots of Rana pipiens were used to study the effects of dendrotoxin (DTX), a specific blocker of a fast activating potassium current (GKf1). 2. Dendrotoxin reduced the ability of myelinated sensory and motor axons to accommodate to a constant stimulus. A depolarizing current step, which normally evoked only one action potential, after dendrotoxin treatment (200-500 nM) produced a train of action potentials. These spike trains lasted 29 +/- 2.8 (SE) ms on average in sensory fibers (n = 18) and 40.2 +/- 4.5 ms in motor fibers (n = 9). 3. After dendrotoxin treatment, in addition to a reduction in the ability to accommodate to a constant stimulus, a slowing in the rate of action potential generation was evident (spike frequency adaptation). 4. Dendrotoxin had no effect on the rising phase of conducted action potentials evoked by peripheral stimulation. Together with a lack of effect on the absolute refractory period, these results indicate that dendrotoxin does not affect sodium channel activity. 5. The steady-state voltage/current relationship was unchanged in response to hyperpolarizing current pulses; however, there was a significant increase in cord resistance in response to depolarizing current steps, demonstrating that DTX decreases outward rectification. 6. A computer model based on Hodgkin and Huxley equations was developed, which included the three voltage-dependent potassium conductances described by Dubois. The model reproduced major experimental results: removal of the conductance, termed GKf1, reduced the accommodation in the early phase of a continuous stimulus, indicating that this current could be responsible for the early accommodation. The hypothesis that the slow potassium conductance GKs regulates late accommodation and action potential frequency adaptation is also supported by the computer model. 7. In summary, these results suggest that in amphibian myelinated sensory and motor axons, the activity of potassium conductances can account for accommodation and adaptation without involvement of sodium conductance activity.

Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons

1993 ◽  
Vol 69 (6) ◽  
pp. 2150-2163 ◽  
Author(s):  
F. Viana ◽  
D. A. Bayliss ◽  
A. J. Berger
Keyword(s):  
Action Potential ◽  
Calcium Influx ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Neonatal Rat ◽  
Repetitive Firing ◽  
Firing Behavior ◽  
Hypoglossal Motoneurons ◽  
Potassium Conductances ◽  
Action Potential Repolarization

1. The role of multiple potassium conductances in action potential repolarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain stem slice preparation of the neonatal rat (0-15 days old). 2. The action potential was followed by two distinct afterhyperpolarizations (AHPs). The early one was of short duration and is termed the fAHP; the later AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (further from EK). In addition, their amplitudes were reduced by high extracellular K+ concentration, suggesting that activation of potassium conductances underlies both phases of the AHP. 3. Prolongation of the action potential and blockade of the fAHP were observed after application of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-AP) (0.1-0.5 mM). Calcium channel blockers had little or no effect on the fAHP or action potential duration. 4. The size of the mAHP was diminished by 1) manganese, 2) lowering external Ca2+, 3) apamin, and 4) intracellular injection of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium activates the potassium conductance that underlies the mAHP. 5. The mAHP was unaffected by nifedipine (20 microM), but was strongly reduced by focal application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium-dependent K+ conductance underlying the mAHP. 6. Repetitive firing properties were investigated by injecting long-duration depolarizing current pulses. Steady-state firing rose linearly with injected current amplitude. The slope of the firing frequency-current (f-I) relationship averaged approximately 30 Hz/nA in control conditions. Blockade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that action potential repolarization and AHPs are due to activation of pharmacologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-dependent, calcium-independent potassium conductance that is TEA- and 4-AP-sensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium-activated potassium conductance greatly influences the normal repetitive firing of neonatal hypoglossal motoneurons.

Effect of Several Cations on Transmembrane Potentials of Cardiac Muscle

1956 ◽  
Vol 186 (2) ◽  
pp. 317-324 ◽  
Author(s):  
Brian F. Hoffman ◽  
E. E. Suckling
Keyword(s):  
Action Potential ◽  
Cardiac Muscle ◽  
Action Potentials ◽  
Time Course ◽  
Pacemaker Activity ◽  
Transmembrane Potentials ◽  
High K ◽  
Intracellular Microelectrodes ◽  
Simultaneous Decrease ◽  
Low K

The effects of changes in the extracellular concentrations of Ca, K and Mg on the transmembrane resting and action potentials of single fibers of the auricle, ventricle and specialized conducting system of the dog heart have been studied by means of intracellular microelectrodes. With respect to Ca, the three tissues exhibit quite different sensitivities. Changes in concentration of this ion alter the time course of the action potential recorded from auricle and ventricle but have little effect on the action potential configuration of the Purkinje fiber. In the latter tissue, on the other hand, pacemaker activity is most strongly enhanced by Ca depletion and excitability is lost at Ca concentrations permitting normal propagation in papillary muscle. The effect of K on the resting transmembrane potential is dependent on the simultaneous Ca concentration. The interrelationship is such that the depolarizing effect of high K is decreased by elevated Ca and the depolarization produced by low K is diminished by low levels of Ca. Changes in the concentration of Mg have little effect on the transmembrane potentials of cardiac muscle unless the level of Ca is low. Under this condition a simultaneous decrease in Mg gives rise to a marked prolongation of the action potential duration of both auricle and ventricle. Some evidence for the basic similarity of the processes underlying repolarization in these three tissues is presented and it is thought the normally encountered differences in their action potentials may be related to the sensitivity of each tissue to extracellular Ca.

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