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Biomedical subjects

G B Frank

Publications and source records attributed to G B Frank.

At least 55 records · Page 3Linked to original sources
PubMed1979

An opiate receptor on frog sciatic nerve axons.

The effect of meperidine (3 X 10(4) M) on the action potential of frog sciatic nerve was examined by means of the double sucrose gap technique. Meperidine decreased the amplitude, maximum rate of depolarization, and maximum rate of repolarization of the action potential but had no effect on the resting potential. This depression in amplitude and maximum rate of rise was partially blocked by naloxone (1 X 10(-8) M) while the maximum rate of depolarization was further depressed. The data suggest that the effect of meperidine is due to two mechanisms, a nonspecific local anaesthetic like effect and an opiate receptor mediated effect.

Action Potentials↗
PubMed1979

Naloxone and naltrexone: actions and interactions at an opiate drug receptor on frog skeletal muscle fibers.

Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of naloxone and naltrexone, two supposedly "pure" opiate antagonists. Both were shown to depress excitability and action potential production when applied in relatively high concentrations. Low naltrexone concentrations antagonized the depression produced by naloxone, but low naloxone concentrations did not antagonize the depression produced by high naltrexone concentrations. Naltrexone also depressed the stimulus-induced increase in potassium conductance (gK) which naloxone did not do. Thus, the naloxone depression is mediated via an opiate drug receptor, whereas naltrexone in high concentrations produces a "local anesthetic-like" depression not involving the opiate drug receptor.

Action Potentials↗
PubMed1978

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

Extracellular and intracellular microelectrode 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 Potentials↗
PubMed1978

Antagonism by phosphate buffer of the twitch loss in isolated muscle fibers produced by calcium-free solutions.

In 37 of 41 isolated frog skeletal muscle fiber preparations (one, two, or three fibers) the twitch was eliminated or reduced to less than 10% of control by exposing the fibers to a O-calcium, bicarbonate-buffered solution for 10 min or less. Replacing the bicarbonate by a phosphate buffer either prevented twitch inhibition or increased the O-calcium exposure time required for its production. It is concluded that surface membrane-bound calcium ions (presumably in the t-tubules) are required to couple the action potential to the mechanical response and that phosphate ions inhibit the loss of the membrane-bound calcium ions into an external calcium-free solution.

Animals↗
PubMed1977

Effects of diphenylhydantoin and phenobarbital on voltage-clamped myelinated nerve.

Diphenylhydantoin (DPH) and phenobarbital (PB) have a selective action in blocking spontaneous activity in nerves made hyperexcitable by lowering the calcium concentration of the bathing medium (Rosenberg, P. and Bartels, E. 1967 J. Pharmacol. Exp. Ther. 155, 532-544.). To investigate this further, we examined the action of DPH and PB on voltage-clamped single myelinated nerves at two different calcium concentrations. In 1.8 mM calcium Ringer, DPH reduced the sodium permeability (PNa) without affecting the potassium conductance (GK) or the voltage-dependent time constants of sodium activation (taum) and inactivation (tauh), and potassium activation (taun). PB was similar to DPH except that in addition to reducing PNa, it shifted taum in the direction of depolarization. When the calcium concentration was lowered to 0.36 mM, the curves relating taum and taun to membrane potential were shifted in the direction of hyperpolarization, as expected. However, the addition of DPH or PB reduced or abolished these shifts. It is suggested that both DPH and PB stabilize hyperexcitable membranes by an action on the parameter m, and that this may contribute to their antiepileptic action.

Action Potentials↗
PubMed1977

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

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-anestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 X 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 X 10(-8) and 2.8 X 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.

Action Potentials↗
PubMed1977

Calcium antagonism of the block in excitation-contraction coupling produced by a urea exposure-removal treatment.

Exposing frog's toe muscles to Ringer's solution made hypertonic with 400 mM urea for 60 min followed by placing the muscles back in Ringer's (urea-removal treatment) completely blocks the twitch without disrupting the surface openings of the T-tubules. The urea-removal treatment also increased the triadic junction width. Placing the muscles in Ringer's with an elevated calcium concentration (5 mM) following exposure to the hyertonic solution prevented the block of the twitch response but not the increase in the triadic junction width. Exposing untreated muscles to Ringer's with 5 mM calcium either had no effect on the twitch on reduced it by 30 percent or less. These results suggest the possibility that increasing the width of the triadic junction decreases the amount of calcium ions reaching the terminal cisternae during an action potential thereby blocking the twitch. Elevating the calcium concentration in the T-tubules would increase the amount of calcium which enters the triadic junction during an action potential and thus antagonize the above effects.

Action Potentials↗
PubMed1975

Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non-specific and opiate drug receptor mediated blockade.

The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro-electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0-35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60-90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(-5) to 3 X 10(-4) mM) at 70-90 min blocked the second phase of the meperidine-induced depression. 4. With lower concentrations of meperidine (0-18 and 0-07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1-5 X 10(-2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non-specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.

Action Potentials↗
PubMed1975

Effects of morphine and meperidine on action potential production in frog's skeletal muscle fibers.

Morphine (3.3 times 10-minus 4 M) and meperidine (8.8 times 10-minus 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.

Action Potentials↗
PubMed1975

Opiate drug receptors on excitable cell membranes.

In drug interaction studies on intact mice it was found that naloxone (3mumoles/kg) antagonized the general central nervous system depressant effects of morphine or meperidine. Higher naloxone doses (0.3 and 0.4 mmoles/kg), like the fullagonists, potentiated the loss of the righting reflex produced by phenobarbital. Naloxone (0.3 to 14 muM) antagonized the depressant effects of morphine or meperidine on the compound action potential of frog's sartorius muscles in vitro. Higher naloxone concentration (ED20=0.3 mM, ED100=3.0mM), like the full agonists, depressed action potential production. These results show that high doses of naloxone can duplicate some effects of morphine or meperidine but at low doses it antagonizes the effects of the full agonists. This would suggest that naloxone is a partial agonist with a very low intrinsic activity. These results also indicate that there are opiate drug receptors on excitable cell membranes and that drug activation of these receptors inhibits action potential production.

Action Potentials↗
PubMed1972

Blockade of the reticulospinal inhibitory pathway by nitrous oxide and tetrodotoxin.

1. The effects of nitrous oxide and tetrodotoxin were investigated on the reticulospinal inhibitory pathway in the acutely decerebrated cat.2. Both agents abolished the reticular inhibition of the segmental reflex potentials before they blocked either the segmental reflex potentials or the reticular facilitation of the reflex potentials.3. These results confirmed the hypothesis that preferential block of the reticulospinal inhibitory pathway might be an important neural mechanism of the excitement stage of anaesthesia.

Animals↗