Differential effects of diazepam on rat hindlimb muscles

1987 ◽  
Vol 65 (9) ◽  
pp. 1856-1863 ◽  
Author(s):  
Michael Chua ◽  
Angela F. Dulhunty
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Calcium Uptake ◽  
Prolonged Exposure ◽  
Resting Membrane Potential ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Isometric Twitch ◽  
Fast Twitch

The effects of diazepam on internal membrane potential and action potentials and the isometric twitch and tetanus have been examined in rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) fibres. Low concentrations of the drug encountered during clinical usage (about 10 μM) had no effect on the membrane electrical properties or contractile properties of the fibres. Higher concentrations of diazepam (100–800 μM) induced changes in action potentials and excitation–contraction coupling but not in the resting membrane potential. After exposure to diazepam there was a rapid, concentration-dependent increase in twitch tension, which was attributed to an effect on excitation–contraction coupling, since the action potential and membrane potential were not altered. Soleus fibres were most sensitive to the potentiating action of diazepam. The decay of the tetanus was prolonged in both types of fibre, which indicated that diazepam blocked calcium uptake by the sarcoplasmic reticulum. Unexpectedly, the decay of isometric twitches was sensitive to diazepam only in soleus fibres, suggesting that calcium uptake was rate-limiting for tension relaxation in slow- but not fast-twitch fibres. The amplitude of the twitch and tetanus fell below control levels after prolonged exposure to diazepam, and there was a parallel reduction in action potential overshoot, especially during tetanic stimulation. Fast-twitch fibres were most susceptible to the depressant effect of diazepam.

scholarly journals The Effect of Aconitine on the Giant Axon of the Squid

1964 ◽  
Vol 47 (4) ◽  
pp. 719-733 ◽  
Author(s):  
W. H. Herzog ◽  
R. M. Feibel ◽  
S. H. Bryant
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Giant Axon ◽  
Membrane Resistance ◽  
Repetitive Stimulation ◽  
Resting Membrane Potential ◽  
Sustained Activity ◽  
Frequency Of Stimulation ◽  
Sodium And Potassium

In the giant axon of Loligo pealii, "aconitine potent" Merck added to the bath (10-7 to 1.25 x 10-6 gm/ml) (a) had no effect on resting membrane potential, membrane resistance and rectification, membrane response to subthreshold currents, critical depolarization, or action potential, but (b) on repetitive stimulation produced oscillations of membrane potential after the spike, depolarization, and decrease of membrane resistance. The effect sums with successive action potentials; it increases with concentration of aconitine, time of exposure, and frequency of stimulation. When the oscillations are large enough and the membrane potential is 51.6 ± SD 1.5 mv a burst of self-sustained activity begins; it usually lasts 20 to 70 sec. and at its end the membrane potential is 41.5 ± SD 1.9 mv. Repolarization occurs with a time constant of 2.5 to 11.1 min. Substitution of choline for external sodium after a burst hyperpolarizes the membrane to -70 mv, and return to normal external sodium depolarizes again beyond the resting membrane potential. The effect of aconitine on the membrane is attributed to an increase of sodium and potassium or chloride conductances following the action potential.

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 temperature on cardiac transmembrane potentials in hibernation

1976 ◽  
Vol 230 (2) ◽  
pp. 403-409 ◽  
Author(s):  
HK Jacobs ◽  
FE South
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Papillary Muscle ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Prolonged Action ◽  
Transmembrane Potentials ◽  
Effects Of Temperature ◽  
And Control ◽  
Potential Parameters

Resting and action potential parameters were measured from papillary muscle isolated from hibernating and control hamsters and from rats. The temperature range of the study was 12-38 degrees C. The decrease in resting membrane potential (Em) with decreasing temperature was significantly less in the hibernation preparations (HH), down to 20 degrees C, than in either the control hamsters or rats. Below 20 degrees C the declines in Em of all preparations were indistinguishable. Action potential magnitude was adequately maintained in HH to 12 degrees C while both control hamster and rat action potentials declined markedly as temperatures were reduced. Both types of hamster preparations showed greatly prolonged action potentials with reduced temperatures as contrasted to a limited prolongation of rat action potentials. The data are suggestive of a membrane modication in hibernation.

Properties of a tonically active, sodium-permeable current in mouse urinary bladder smooth muscle

2004 ◽  
Vol 286 (6) ◽  
pp. C1246-C1257 ◽  
Author(s):  
Kevin S. Thorneloe ◽  
Mark T. Nelson
Keyword(s):  
Membrane Potential ◽  
Urinary Bladder ◽  
Action Potential ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Bladder Smooth Muscle ◽  
Voltage Dependent ◽  
Urinary Bladder Smooth Muscle

Urinary bladder smooth muscle (UBSM) elicits depolarizing action potentials, which underlie contractile events of the urinary bladder. The resting membrane potential of UBSM is approximately −40 mV and is critical for action potential generation, with hyperpolarization reducing action potential frequency. We hypothesized that a tonic, depolarizing conductance was present in UBSM, functioning to maintain the membrane potential significantly positive to the equilibrium potential for K+ ( EK; −85 mV) and thereby facilitate action potentials. Under conditions eliminating the contribution of K+ and voltage-dependent Ca2+ channels, and with a clear separation of cation- and Cl−-selective conductances, we identified a novel background conductance ( Icat) in mouse UBSM cells. Icat was mediated predominantly by the influx of Na+, although a small inward Ca2+ current was detectable with Ca2+ as the sole cation in the bathing solution. Extracellular Ca2+, Mg2+, and Gd3+ blocked Icat in a voltage-dependent manner, with Ki values at −40 mV of 115, 133, and 1.3 μM, respectively. Although UBSM Icat is extensively blocked by physiological extracellular Ca2+ and Mg2+, a tonic, depolarizing Icat was detected at −40 mV. In addition, inhibition of Icat demonstrated a hyperpolarization of the UBSM membrane potential and decreased the amplitude of phasic contractions of isolated UBSM strips. We suggest that Icat contributes tonically to the depolarization of the UBSM resting membrane potential, facilitating action potential generation and thereby a maintenance of urinary bladder tone.

Biphasic effects of hyposmotic challenge on excitation-contraction coupling in rat ventricular myocytes

2000 ◽  
Vol 279 (4) ◽  
pp. H1963-H1971 ◽  
Author(s):  
F. Brette ◽  
S. C. Calaghan ◽  
S. Lappin ◽  
E. White ◽  
J. Colyer ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Prolonged Exposure ◽  
Ventricular Myocytes ◽  
Negative Inotropic Effect ◽  
Short Exposure ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Rat Ventricular Myocytes ◽  
Intracellular Ca

The effects of short (1 min) and long (7–10 min) exposure to hyposmotic solution on excitation-contraction coupling in rat ventricular myocytes were studied. After short exposure, the action potential duration at 90% repolarization (APD90), the intracellular Ca2+concentration ([Ca2+]i) transient amplitude, and contraction increased, whereas the L-type Ca2+ current ( I Ca,L) amplitude decreased. Fractional sarcoplasmic reticulum (SR) Ca2+ release increased but SR Ca2+ load did not. After a long exposure, I Ca,L, APD90, [Ca2+]i transient amplitude, and contraction decreased. The abbreviation of APD90 was partially reversed by 50 μM DIDS, which is consistent with the participation of Cl− current activated by swelling. After 10-min exposure to hyposmotic solution in cells labeled with di-8-aminonaphthylethenylpyridinium, t-tubule patterning remained intact, suggesting the loss of de-t-tubulation was not responsible for the fall in I Ca,L. After long exposure, Ca2+ load of the SR was not increased, and swelling had no effect on the site-specific phosphorylation of phospholamban, but fractional SR Ca2+ release was depressed. The initial positive inotropic response to hyposmotic challenge may be accounted for by enhanced coupling between Ca2+ entry and release. The negative inotropic effect of prolonged exposure can be accounted for by shortening of the action potential duration and a fall in the I Ca,L amplitude.

Suppressive effect of acetylcholine on action potentials of canine paranodal fibers

1986 ◽  
Vol 251 (4) ◽  
pp. H710-H715
Author(s):  
W. W. Tse
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Conduction Block ◽  
Suppressive Effect ◽  
Resting Membrane Potential ◽  
Av Conduction ◽  
Av Conduction Block

The canine atrioventricular (AV) junction comprises three major tissues: paranodal fibers (PNF), AV node (AVN), and His bundle (HB). In the present study, dissection-exposed, in vitro canine AV junctional preparations were used. The object of the study was to determine whether the PNF or AVN was more sensitive to the suppressive effect of acetylcholine (ACh). In five experiments these tissues were stimulated antegradely and retrogradely, and their action potentials were recorded simultaneously under the influence of ACh (0.5 micrograms/ml). Results indicated the PNF were more sensitive to the suppressive effect of ACh than were the AVN. In another group of 13 experiments, the effects of ACh at 0.05-0.3 micrograms/ml on rate of rise of phase 0 of action potentials (Vmax), peak potential, resting membrane potential, and action potential duration of the PNF were determined. Results indicated that ACh exerted a strong suppressive effect on Vmax and amplitude of the action potentials and had little effect on the resting membrane potential and action potential duration of the PNF. In 10 of 13 preparations, ACh also suppressed the response of PNF, resulting in generation of one action potential to every two stimuli. In conclusion, these findings suggest that PNF could be the tissue responsible for vagal-induced AV conduction block.

scholarly journals Distinctive Neurophysiological Properties of Embryonic Trigeminal and Geniculate Neurons in Culture

2002 ◽  
Vol 88 (4) ◽  
pp. 2058-2074 ◽  
Author(s):  
Arturas Grigaliunas ◽  
Robert M. Bradley ◽  
Donald K. MacCallum ◽  
Charlotte M. Mistretta
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Target Tissue ◽  
Extrinsic Factors ◽  
Single Action ◽  
Trigeminal Neurons ◽  
Ganglion Neurons ◽  
Passive Membrane

Neurons in trigeminal and geniculate ganglia extend neurites that share contiguous target tissue fields in the fungiform papillae and taste buds of the mammalian tongue and thereby have principal roles in lingual somatosensation and gustation. Although functional differentiation of these neurons is central to formation of lingual sensory circuits, there is little known about electrophysiological properties of developing trigeminal and geniculate ganglia or the extrinsic factors that might regulate neural development. We used whole cell recordings from embryonic day 16 rat ganglia, maintained in culture as explants for 3–10 days with neurotrophin support to characterize basic properties of trigeminal and geniculate neurons over time in vitro and in comparison to each other. Each ganglion was cultured with the neurotrophin that supports maximal neuron survival and that would be encountered by growing neurites at highest concentration in target fields. Resting membrane potential and time constant did not alter over days in culture, whereas membrane resistance decreased and capacitance increased in association with small increases in trigeminal and geniculate soma size. Small gradual differences in action potential properties were observed for both ganglion types, including an increase in threshold current to elicit an action potential and a decrease in duration and increase in rise and fall slopes so that action potentials became shorter and sharper with time in culture. Using a period of 5–8 days in culture when neural properties are generally stable, we compared trigeminal and geniculate ganglia and revealed major differences between these embryonic ganglia in passive membrane and action potential characteristics. Geniculate neurons had lower resting membrane potential and higher input resistance and smaller, shorter, and sharper action potentials with lower thresholds than trigeminal neurons. Whereas all trigeminal neurons produced a single action potential at threshold depolarization, 35% of geniculate neurons fired repetitively. Furthermore, all trigeminal neurons produced TTX-resistant action potentials, but geniculate action potentials were abolished in the presence of low concentrations of TTX. Both trigeminal and geniculate neurons had inflections on the falling phase of the action potential that were reduced in the presence of various pharmacological blockers of calcium channel activation. Use of nifedipine, ω-conotoxin-MVIIA and GVIA, and ω-agatoxin-TK indicated that currents through L-, N-, and P/Q- type calcium channels participate in the action potential inflection in embryonic trigeminal and geniculate neurons. The data on passive membrane, action potential, and ion channel characteristics demonstrate clear differences between trigeminal and geniculate ganglion neurons at an embryonic stage when target tissues are innervated but receptor organs have not developed or are still immature. Therefore these electrophysiological distinctions between embryonic ganglia are present before neural activity from differentiated receptive fields can influence functional phenotype.

Electrical and mechanical responses of uterine smooth muscle during anaphylaxis in vitro

1958 ◽  
Vol 196 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Seymour Katsh ◽  
Jean M. Marshall
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Specific Antigen ◽  
Resting Membrane Potential ◽  
Uterine Smooth Muscle ◽  
Mechanical Responses ◽  
Spontaneous Contractions

Female guinea pigs were injected with antigen (homologous sperm or ovalbumin) and 14–28 days later ileal segments and both uterine horns were removed. The ileal segments and one of the uterine horns from each animal were tested for responses to drugs, as well as to nonspecific and specific antigen; responses were recorded by means of a kymograph and muscle lever. The contralateral cornua were tested with nonspecific and with specific antigen as well as with drugs; responses were detected and recorded with intracellular electrodes and a mechanotransducer. The notable findings relative to the electronic studies were: within 1–2 minutes following exposure of the sensitized uterus to specific antigen there occurred a) a diminution in resting membrane potential; b) a sudden burst of action potential spikes; c) a contraction of the musculature which was of greater amplitude and of longer duration than those of the spontaneous contractions; d) during the sustained contracture phase, the rate of discharge of action potential spikes was higher than that accompanying spontaneous contractions. After desensitization, specific antigen was without effect. No effect of nonspecific antigen was observed in any of the preparations. After stimulating with specific antigen or with drugs, additional action potentials arose before repolarization from the previous action potential was completed.

Overexpression of human β2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes

2004 ◽  
Vol 287 (3) ◽  
pp. H1029-H1038 ◽  
Author(s):  
Scott A. Grandy ◽  
Eileen M. Denovan-Wright ◽  
Gregory R. Ferrier ◽  
Susan E. Howlett
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Action Potential ◽  
Adrenergic Receptors ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Wild Type ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Excitation ◽  
Action Potential Configuration

This study investigated cardiac excitation-contraction coupling at 37°C in transgenic mice with cardiac-specific overexpression of human β2-adrenergic receptors (TG4 mice). In field-stimulated myocytes, contraction was significantly greater in TG4 compared with wild-type (WT) ventricular myocytes. In contrast, when duration of depolarization was controlled with rectangular voltage clamp steps, contraction amplitudes initiated by test steps were the same in WT and TG4 myocytes. When cells were voltage clamped with action potentials simulating TG4 and WT action potential configurations, contractions were greater with long TG4 action potentials and smaller with shorter WT action potentials, which suggests an important role for action potential configuration. Interestingly, peak amplitude of L-type Ca2+ current ( ICa-L) initiated by rectangular test steps was reduced, although the voltage dependencies of contractions and currents were not altered. To explore the basis for the altered relation between contraction and ICa-L, Ca2+ concentrations were measured in myocytes loaded with fura 2. Diastolic concentrations of free Ca2+ and amplitudes of Ca2+ transients were similar in voltage-clamped myocytes from WT and TG4 mice. However, sarcoplasmic reticulum (SR) Ca2+ content assessed with the rapid application of caffeine was elevated in TG4 cells. Increased SR Ca2+ was accompanied by increased frequency and amplitudes of spontaneous Ca2+ sparks measured at 37°C with fluo 3. These observations suggest that the gain of Ca2+-induced Ca2+ release is increased in TG4 myocytes. Increased gain counteracts the effects of decreased amplitude of ICa-L in voltage-clamped myocytes and likely contributes to increased contraction amplitudes in field-stimulated TG4 myocytes.

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