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Biomedical subjects

R L Volle

Publications and source records attributed to R L Volle.

At least 37 records · Page 2Linked to original sources
PubMed1981

Cyclic guanosine 3':5'-monophosphate accumulation and 45Ca-uptake by rat superior cervical ganglia during preganglionic stimulation.

Repetitive preganglionic nerve stimulation increases cyclic guanosine 3':5'-monophosphate (cGMP) content in rat superior cervical ganglia by a mechanism requiring Ca++ but resistant to blockade by cholinergic receptor antagonists. Similarly, 45Ca-uptake during prolonged preganglionic nerve stimulation is unaffected by hexamethonium or atropine. These findings indicate that nerve stimulation increases cGMP accumulation and 45Ca-uptake by a noncholinergic mechanism Substance P, met-enkephalin and luteinizing hormone-releasing factor have little or no effect on cGMP content. By contrast, bethanechol causes a 3-fold increase in cGMP content and postganglionic cell firing. Thus, as reported by others, muscarinic receptor activation increases ganglionic cGMP[. 4-Aminopyridine causes an increase in cGMP of resting ganglia that requires Ca++ and the nerve terminal is blocked by tetrodotoxin but unaffected by atropine or hexamethonium. Ouabain also increases ganglionic cGMP content by a process that requires Ca++ and the nerve terminals. Like preganglionic nerve stimulation, 4-aminopyridine and ouabain cause cGMP accumulation in the nerve terminals or in the ganglion cells as a consequence of releasing a noncholinergic transmitter. The uptake of Ca++ by ganglion cells is not an adequate stimulus for cGMP accumulation because the nicotinic receptor agonist dimethylphenylpiperazinium increases 45Ca-uptake but has no effect on cGMP formation in ganglia.

4-Aminopyridine↗
PubMed1981

Characterization of end-plate conductance in transected frog muscle: modification by drugs.

Cutaneous pectoris muscles of Rana pipiens were transected distal to the innervated region. Within 10 min, membrane potentials (Em's) of -33 +/- 2.5 mV and end-plate potentials (3-15 mV) were recorded unaccompanied by muscle action potentials or twitch. The fall in Em was associated with a net loss of [K+]i and a net gain of [Na+]i. Although input resistance fell by 50% and the space constant was slightly reduced in the transected muscle fibers, end-plates could be adequately voltage-clamped with two microelectrodes. End-plate currents (e.p.c.s) with rise times of 350 to 700 musec were recorded as a function of holding potential (Vm). The current-voltage relationship of peak e.p.c.s over the range of -70 to +20 mV was linear and the reversal potential (-6.6 +/- 2.2 mV) was the same as that found for intact muscle fibers. The decay phase of e.p.c.s could be described as a single exponential at all Vm's and had a voltage and temperature dependence similar to that described for e.p.c.s of glycerol-treated muscles. Tubocurarine (0.3 microM) caused a significant decrease in the time constant (tau) of e.p.c. decay and e.p.c. amplitude. The depression of e.p.c. amplitude by tubocurarine was reversed by 4-aminopyridine while the decrease of tau was not. Atropine (10(-4) M) caused a monotonic shortening of e.p.c.s at a Vm of -90 mV but e.p.c.s recorded at +50 mV were biphasic. Lidocaine, a quaternary nitrogen analog of lidocaine (QX314), lobeline and hexafluorenium were studied also in transected muscle and their effects on the parameters of e.p.c. are described. Both lobeline (50 microM) and hexafluorenium caused a decrease of tau and eliminated the voltage dependence of tau at negative Vm's. The transected muscle can be used for the study of conductance kinetics of end-plate and for the study of drug action uncomplicated by the presence of other drugs of Mg++ to eliminate contraction.

4-Aminopyridine↗
PubMed1980

Effects of McN-A-343, a cholinomimetic drug, on endplate currents in the frog.

The muscarinic ganglion stimulating agent, McN-A-343 has unusual blocking actions on endplate currents (EPCs) at frog neuromuscular junctions. McN-A-343 caused depolarization by a curare-sensitive process, blocked neuromuscular transmission, depressed EPCs and reduced the time for EPC decay. These results are explained best by a nicotinic agonist action of McN-A-343 on the acetylcholine receptor to cause ion flow and the blockade by McN-A-343 of the open ion channels. The actions of McN-A-343 are similar to those of decamethonium (C-10) described by others. Unlike C-10, however, McN-A-343 did not alter the exponential character of the EPC or alter the voltage dependency of the EPC. The prototypical nicotinic agonist, dimethylphenylpiperazinium had no effect on EPC parameters of endplate clamped at -90mV.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1980

An attempt to distinguish between the actions of neuromuscular blocking drugs on the acetylcholine receptor and on its associated ionic channel.

The effects of lobeline and tubocurarine on the voltage-clamped endplates of frog sartorius and cutaneous pectoris muscles were examined at room temperature (20-23 degrees C). Like tubocurarine, lobeline causes nondepolarizing neuromuscular blockade. The half-time of decay (t((1/2))) of endplate currents (e.p.c.s) recorded at a holding potential (V(m)) of -90 mV was significantly shorter in endplates treated with lobeline (50 muM; mean t((1/2)) +/- SEM = 0.41 +/- 0.02 ms) or tubocurarine (11.4 muM; t((1/2)) = 0.64 +/- 0.04 ms) than in those treated with Mg(2+) (13 mM; t((1/2)) = 1.39 +/- 0.11 ms) or a low concentration of tubocurarine (3 muM; t((1/2)) = 0.87 +/- 0.05 ms). Similarly, lobeline (10 muM) shortened the t((1/2)) of untreated miniature e.p.c.s by 35%; tubocurarine, however, abolished miniature e.p.c.s at the concentration required to observe its actions on e.p.c. decay kinetics. The t((1/2)) of e.p.c.s recorded from preparations treated with Mg(2+) (13 mM), tubocurarine at low concentrations (3 muM), or untreated miniature e.p.c.s was logarithmically related to V(m), being slower at more hyperpolarized values. By contrast, the t((1/2))s of e.p.c.s recorded in either lobeline (50 muM) or tubocurarine (11.4 muM) were independent of voltage in the range -150 to -80 mV. The ability of lobeline to shorten t((1/2)) and to remove the voltage dependence of t((1/2)) was partially antagonized by Mg(2+) (13 mM). As expected, when lobeline or tubocurarine was removed from the bath or when acetylcholine release from the motor nerve terminals was increased by 4-aminopyridine (20 muM) and Ca(2+) (10 mM) (in the presence of lobeline or tubocurarine), the amplitude of e.p.c.s increased as a function of time. However, the t((1/2)) of the decay phase of the e.p.c.s remained shortened (i.e., unaltered from the earlier treatment). These results suggest that both tubocurarine and lobeline have at least two distinct postjunctional actions including: (i) a block of the acetylcholine receptor and (ii) a block of the ionic channel associated with the acetylcholine receptor.

Animals↗
PubMed1979

Transmission blockade and stimulation of ganglionic adenylate cyclase by catecholamines.

Isolated rat superior cervical ganglia treated with isoproterenol and related drugs show an increase in ganglionic cyclic adenosine 3':5'-monophosphate (cAMP) and a block of transmission. For isoproterenol, the maximum increase in cAMP occurred at 1 X 10(-6) M, a concentration without effect on transmission. Approximately 5 X 10(-4) M isoproterenol was required to reduce the ganglionic compound action potential by 50%. Dopamine, in contrast to isoproterenol, had no effect on the content of cAMP but depressed transmission. The maximum increase in cAMP produced by norepinephrine occurred with 5 X 10(-4) M, a concentration that reduced transmission by approximately 35%. The effects of isoproterenol on adenylate cyclase and transmission were prevented either by practolol (10(-4) M) or phentolamine (10(-5) M). Dopamine-induced blockade of transmission was antagonized by phentolamine (10(-5) M). Whereas the blockade of transmission by norepinephrine was antagonized by practolol (10(-5) M) or phentolamine (10(-5) M), the stimulation of adenylate cyclase by norepinephrine was prevented by practolol (10(-4) M) but not by phentolamine (10(-5) M). These results show that the blockade of transmission and stimulation of adenylate cyclase are unrelated in rat ganglia and that adrenergic receptor classification is ambiguous. The role of adenylate cyclase in ganglia is unclear.

Adenylyl Cyclases↗
PubMed1979

Nicotinic, muscarinic and adrenergic receptors in a parasympathetic ganglion.

Transmission in submandibular ganglia of hamsters was blocked by hexamethonium and dimethylphenylpiperazinium. Dimethylphenylpiperazinium caused depolarization and decreased membrane resistance (Rm). The muscarinic agonist, bethanechol (BCh) caused depolarization of some cells and hyperpolarization of others. Regardless of the change in membrane potential, BCh always increased Rm. Since the responses to BCh persisted in the absence of [Ca++]0, it was concluded that BCh acted directly on the ganglion cells and did not depend upon a transsynaptic process. All responses to BCh were prevented by atropine. The evidence suggests that the ganglion cells possess muscarinic receptors. Like BCh, norepinephrine (NE) either depolarized or hyperpolarized the ganglion cells. There was no relationship between the blockade of transmission by NE and the effect of NE on the membrane potential. The responses to NE were prevented by dihydroergotamine, suggesting the presence of alpha adrenergic receptors on the ganglion cells.

Acetylcholine↗
PubMed1978

Responses of the rat superior cervical ganglion in vitro to isoprenaline and bethanechol.

The effects of isoprenaline were studied in isolated rat superior cervical ganglia. Intracellularly recorded excitatory postsynaptic potentials were depressed by isoprenaline in concentrations of 10(-5) to 10(-4)M. In 13 out of 17 cells, isoprenaline caused ganglionic hyperpolarization (mean, 4mV). Changes in the amplitude and contour of antidromic action potentials caused by isoprenaline could be accounted for by the increased membrane potential. A slight increase in membrane input resistance from 44--50.2 megohms (mean values) occurred in about half of the cells. Activation of an ion pump by isoprenaline was suggested by the finding that the hyperpolarization did not occur when the bathing solution contained ouabain (10(-5)M) or lacked Na+ or K+. Characterization of the isoprenaline effects by the use of alpha and beta adrenergic blocking drugs was not possible because of the direct depressant effects of the antagonists. The muscarinic agonist bethanechol (2.5 X 10(-5) to 2.5 X 10(-4)M) caused ganglionic depolarization and increased input membrane resistance (42--52 megohms) during depolarization in each of the cells tested. The ganglionic responses to bethanechol were prevented by atropine.

Action Potentials↗
PubMed1978

The increase in spontaneous transmitter release produced by beta-bungarotoxin and its modification by inorganic ions.

The excitatory phase of the biphasic action on transmitter release of the neurotoxin, beta-bungarotoxin (beta-BuTX; 0.5 microgram ml-1), was studied on miniature end-plate potentials (MEPPs) at frog sciatic nerve-sartorius muscle junctions. The most common type of excitatory response was characterized by a continuous increase in MEPP frequency that reached a plateau; a less common form was characterized by irregular episodic bursts of firing. There was a direct relationship between toxin activity and [K+]O (2.5-10.0 mM) with virtually no effect of the toxin at normal [K]O+ at the concentration of toxin used. In the absence of Mg++, there was a paradoxical inverse relationship between toxin activity and [Ca++]O (0.5-4.0 mM) at higher [K+]O. However, in the presence of 1.0 mM Mg++ the increased MEPP frequency produced by beta-BuTX was independent of [Ca++]O. The action of beta-BuTX was very sensitive to blockade by Mg++. Toxin activity was demonstrated in a Sr++-containing, Ca++-free solution, but not in a Mg++-containing, Ca++-free solution. It is probable that beta-BuTX causes a slight depolarization of the nerve terminals by a mechanism not sensitive to blockade by tetrodotoxin and that the ability of beta-BuTX to depolarize the terminals can account for the enhancement of the response by raising [K+]O and the depression of the response by Mg++. Alternatively, beta-BuTX could be producing its effects by some, as yet undefined, direct action on the release process.

Action Potentials↗
PubMed1977

Transmitter mobilization at the frog neuromuscular junction.

During frequency facilitation of frog neuromuscular junctions depressed by Mg++, the relationship between quantal content (m) and frequency of stimulation (0.5 to 8 Hz) is exponential. The slope of the relationship (k) reflects transmitter mobilization and the zero-frequency intercept (mo) reflects the basic release process. The catecholamines, tetraethylammonium, guanidine and raised [Ca++]o increased mo but had no effect on k. At junctions where release ranged from 200 to 500 quanta sec-1 during steady-state conditions, this result was interpreted to mean that the drugs increased both transmitter release and mobilization. An analog of hemicholinium-3, DMAE, depressed k, reflecting the ability of DMAE to depress transmitter mobilization. The alternative possibility that the frequency facilitation relationship was altered by effects of the drugs on the number of activated release sites was also considered.

Animals↗
PubMed1976

Quantal parameters of transmission at the frog neuromuscular junction.

Estimates of quantal release parameters at frog neuromuscular junctions showed that alterations in [Ca2+]o affected m (number of quanta), p (probability of quantal release) and n (stores of quanta available for release). The effect of [Ca2+]o depended upon the initial value for p. When p was low, raising [Ca2+]o increased m and p, but not n. However, when p was large, raising [Ca2+]o had no further effect on p but increased m and n. During prolonged repetitive nerve stimulation to cause a decrease in m, n was decreased and p was increased. This finding was attributed to a failure of transmitter mobilization to maintain the stores of transmitter available for release.

Acetylcholine↗
PubMed1976

Effects of physiologic alterations on binomial transmitter release at magnesium-depressed neuromuscular junctions.

1. Transmitter release from Mg2+-treated frog neuromuscular junctions can be described by binomial statistics. Good agreement between the observed amplitude-frequency distribution of e.p.p.s. and that predicted by binomial statistics is observed with relatively low concentrations of Mg2+. Conversely, good agreement is found with Poisson predictions when higher concentrations of Mg2+ are used to depress transmission. 2. Binomial analysis at these junctions shows that Mg2+ reduces quantal content (m), the probability of release (p) and to a lesser extent the available stores of transmitter (n). Raising Ca2+ causes an increase in n and p and a small but significant increase in n. K+ increases m and p but not n. 3. During 'frequency-facilitation' (1-6 Hz), e.p.p.s., m and n are increased but p is unaffected. 4. It is concluded that binomial statistics can be used to estimate the quantal parameters of transmitter release and that these parameters can be identified as discrete entities.

Animals↗
PubMed1976

Statistical parameters of transmitter release at frog neuromuscular junctions treated with guanidine or tetraethylammonium.

Transmitter release at Mg++ -depressed frog neuromuscular junctions can be described using binomial statistics. The number of quanta (m) released by the nerve terminal action potential is directly proportional to the mean probability (p) that a quantum will be released and the number of quanta available for release (n). Guanidine or tetraethylammonium (TEA) increased m and n, but had no effect on p. At junctions depressed by d-tubocurarine, both compounds enhanced the amplitude of the initial end-plate potential, caused an accelerated rate of fade of end-plate potential amplitudes and raised the steady-state level of end-plate potential amplitude. This finding was interpreted to mean that guanidine and TEA increased transmitter mobilization and may be related to the increase by the compounds of the parameters n. If so, then the data support the idea that n represents the number of quanta available for release rather than the number of transmitter release sites in the terminal membrane. Neither compound affected the power relationship between [Ca++]o and transmitter release. When plotted on a double logarithmic basis, the slope of the line relating [Ca++]o to increased transmitter release was 3.7, a relationship not altered by the drugs. Thus, the compounds had no effect on the fundamental interaction between Ca++ and transmitter release sites. In contrast to [Ca++]o, the power relationship between increased transmitter release and the concentration of drug in the bathing solution was 0.69 for guanidine and 0.84 for TEA. Because of this finding, it was concluded that the compounds increased transmitter release by mechanisms other than or in addition to increasing Ca++ conductance.

Animals↗
PubMed1975

Quantal release parameters during fade of endplate potentials.

An analog of hemicholinium-3 caused the fade of endplate potentials during repetitive stimulation at low rates. The quantal parameters of release were estimated during steady-state conditions before and in the presence of the drug. The fade of EPP's was associated with a decrease in quantal content (m). The decrease in m was, in turn, associated with a decrease in the binomial parameter n and an increase in the binomial parameter p. The changes in n and p are discussed in relation to available stores of transmitter and the probability of transmitter release.

Action Potentials↗