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The control of membrane ionic currents by the membrane potential of muscle.

Comparisons between electrotronic potentials and certain predicted curves allow the identification of the membrane potential at which the sodium and potassium currents are switched on in frog sartorius. The activation potentials (the membrane potentials at which the ionic currents are great enough to be resolved by the method) are functions of the resting potential and time but not of ionic concentration. In the normal fiber, the activation potential for sodium lies nearer the resting potential and depolarizations set off sodium currents and action potentials. Below a resting potential of 55 to 60 mv. sodium activation is lost and conduction is impossible. A tenfold increase of calcium concentration lowers (moves further from the resting potential) the sodium activation potential by 20 to 25 mv. whereas the potassium activation potential is lowered by only 15 mv. Certain consequences of this are seen in the behavior of the muscle cell when it is stimulated with long duration shock.

Action Potentials↗

Transmembrane K+, Na+, and Cl- permeability and conductance changes in the frog sartorius fibres following ouabain and zero [K+]o treatment.

Changes in the K+, Na+, and Cl- permeabilities (P) and conductances (g) of the intact frog sartorius fibre membrane following ouabain or zero [K+]o treatment were calculated from intrafibre activity and whole muscle electrolyte changes. Conventional equations relating ionic fluxes to resting potential (E), ionic gradient potential, and internal and external ionic activities were used. Both treatments produced a three- to five-fold increase in PNa and gNa. In addition, ouabain produced a fivefold increase in PK (and gK) and a small decrease in PCl (and gCl), whereas zero [K+]o produced a 60% reduction in PK, a 90% reduction in gK, and a threefold increase in PCl (and gCl). When the two treatments were combined, the P and g changes were paradoxical, suggesting that the ouabain-induced increase in gK and the zero [K+]o-induced decrease in gK were occurring but in different channels (or carriers). During ouabain treatment, E reflects mainly the transmembrane K+ gradient potential; during zero [K+]o treatment, E reflects mainly the Cl- gradient potential. Despite channel (or carrier) specificity, it appears that all three ionic permeabilities are altered during the perturbations.

Animals↗

High energy phosphate utilization for work production and tension maintenance in frog muscle.

Frog (Rana esculenta, L.) gastrocnemii (161 pairs) or sartorii (8 pairs) were stimulated by intermittent tetani at 10 degrees C (20 Hz, supramaximal intensity, N2 atmosphere) isometrically (IM) or isotonically (IT) for various durations (6-30 s) at different tensions (0.05-1.00 Po = maximal IM tension at resting length, lo). The energy expenditure (E) was measured from ATP and phosphocreatine breakdown and the high energy phosphate equivalent of lactic acid production. Both in IM and IT conditions, E was found to be a linear function of the summated tetanus duration (t): E = a + b t, where b is the energy cost of tension maintenance. For the gastrocnemius, both in IM and IT, b was independent of the tension developed and equal to 0.45 mumol approximately P.g-1.s-1, whereas for the sartorius b was tension-dependent varying between 0.58 and 0.28 mumol approximately P.g-1.s-1 for Po and 0.18 Po, respectively. The constancy of the b value in muscles with pennate structure may be tentatively attributed, at least in part, to the greater internal energy dissipation, regardless of the tension developed. The term a of the above equation is due to all time-independent processes of muscle contraction, i.e.: (1) activation energy; (2) internal work and (3) external work (in IT only). Based on the measured value of a and on the work performed, the mechanical equivalent of approximately P splitting was calculated as 17.7 kJ.mol-1, a figure close to that previously obtained on frog sartorius (16.7 kJ.mol-1) and dog gastrocnemius (19.2 kJ.mol-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Soft tissue anatomy of proximal femoral focal deficiency.

The soft tissue anatomy of Aitken types A, B, C, and D proximal femoral focal deficiency (PFFD) was examined by magnetic resonance imaging (MRI). A characteristic pattern of soft tissue abnormalities is described. All muscles were present, but most were smaller than their normal counterparts. The exception was the obturator externus muscle, which was elongated and remained muscular almost up to its insertion. In type A PFFD, it is straight; in types B, C, and D PFFD, it is L-shaped. The sartorius is hypertrophied.

Adolescent↗

Desensitization shortens the high-quantal-content endplate current time course in frog muscle with intact cholinesterase.

1. The desensitization induced by bath-applied carbachol or acetylcholine (ACh) and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with intact synaptic acetylcholinesterase (AChE). 2. The reduction in the density and number of postsynaptic receptors produced by desensitization lowered the amplitude of the endplate currents (EPCs) and shortened the EPC decay when the quantal content (m) of the EPC was about 170 and when multiple release of quanta at single active zones was highly probably. The shortening of high-quantal-content EPCs persisted for at least 15 min after the wash-out of agonists, at a time when the amplitude had recovered fully. 3. The decay times of the low-quantal-content EPCs recorded from preparations pretreated with 5 mM Mg2+ (m approximately 70) and single-quantum miniature endplate currents (MEPCs) were not affected by carbachol, ACh or proadifen. 4. The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE. 5. It is assumed that high-quantal-content EPCs increase the incidence of multiple quanta release at single active zones and the probability of repetitive binding of ACh molecules which leads to EPC prolongation. The shortening which persists after complete recovery of the amplitude during wash-out of the exogenous agonist is probably due to 'trapping' of ACh molecules onto rapidly desensitized receptors and the reduced density of functional AChRs during the quantum action.

Acetylcholine↗

Growth and muscle defects in mice lacking adult myosin heavy chain genes.

The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical. We describe mice carrying null mutations in each of two predominant adult fast MyHC genes, IIb and IId/x. Both null strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest distribution of expression, the phenotypes of IIb null mutants are generally milder than in the MyHC-IId/x null strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histological defects are completely different for null expression of the two genes. Most striking is that while both null strains exhibit physiological defects in isolated muscles, the defects are distinct. Muscle from IIb null mice has significantly reduced ability to generate force while IId null mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology.

Age Factors↗

[Influence of various agents on the magnitude of intracellular local changes of resistance].

The effect of local changes of resistance that was earlier described in horizontal cells and muscle fibres appears in response to the changes of membrane potential. The local resistance decreased with depolarization and increased with hyperpolarization. In experiments on musculus sartorius of the frog it is shown that the magnitude of the effect increased with cooling to 0 degrees C and reversibly abolished with warming to 30--35 degrees. The effect of local changes of resistance was diminished also by ethanol (5%) and with the increase of pH of perfusing solution to 9--10, the decrease of pH to 3,5--4 increased the effect. Preincubation of the muscle in solution containing colchicine or dinitrophenol did not abolish the effect of local changes of resistance. The nature of the structure responsible for the effect is discussed.

Animals↗

Isometric muscle contraction and the active state: an analog computer study.

From Sandow's excitation-contraction coupling hypothesis and reasonable assumptions I obtain the kinetics of the active state, (AS), and thence, via empirical equations for series elastic and contractile components for frog sartorius around 20 degrees C, the tension, P, and dP/dt vs. time. Assumptions: (a) Rate of Ca(+2) injection is proportional to the Ca gradient, and a permeability, which increases from zero to a limit as the membrane potential rises above a threshold. (b) Released Ca(+2) is bound by the "muscle machinery," M, and removed by a carrier pump. (c) The AS is proportional to the concentration of Ca-M. The kinetic pattern depends mainly upon the mechanism; the time scale was fixed by the amount of Ca(+2) injected. Depending upon the time course and repetition pattern chosen for the action potential, I obtain P and dP/dt, that agree well with experiment, for normal, potentiated, and summed twitches, tetani, and tension redevelopment after a quick release. Upon excitation the AS rises rapidly to 88%, declines thereafter in twitches, but rises slowly in unfused fashion toward 100% in tetani. The knee in dP/dt marks the first maximum in the AS. Potentiators should raise it in tetani as well as in twitches. Velocity and dP/dt show a much higher fusion frequency than P. The model integrates diverse observations. It may be tested by measuring tension and intramyofibrillar Ca(+2) under controlled depolarization.

Animals↗

The sartorius myocutaneous island flap.

The vascular supply to the distal part of sartorius m. was studied in 37 limbs by dissection under magnification and after black ink and latex injections. The muscle or myocutaneous island flap pedicled on the saphenous artery (SA) is supplied by a retrograde circulation through anastomoses of the SA with the perforating branches of the posterior tibial artery and the medial inferior genicular artery. Three different vascular patterns were defined. Retrograde injection also showed good perfusion of the SA. The flap is useful for covering around the knee, the proximal and middle thirds of the lower leg, and the end of the amputation stump. Raising of the flap has not resulted in any functional or cosmetic defect. Eighteen operations have so far been performed, six using the muscle island flap and twelve using the myocutaneous island flap, and all survived completely.

Humans↗

Computer added locomotion by implanted electrical stimulation in paraplegic patients (SUAW).

Paraplegia means a live long sentence of sensory loss, paralysis and dependence with approximately 1000 new victims in every European country every year and 11.500 new traumatic SCI cases in the US. respectively. Sixty percent are injured before age 30. More than 90% of SCI victims may survive with nearly normal experience of live. Most patients will recover somewhat from SCI over time but no patient who remained plegic for one year regains voluntary motor function after that time period. Despite remarkable efforts and recent achievements in rehabilitation no treatment can be recommended so far to enhance functional recovery and restoring locomotion in paraplegic humans. FES as a technical compensation has become therefore a challenging treatment to restore muscle function and to prevent atrophy and to improve mobility and quality of life at the same time. In paraplegics FES could be the basis to restore locomotion. One of the advantages of an implanted FES version (neuroprosthesis) is that the FES system, electrodes, and cables remain permanently implanted within the body, so that the patient can stay without cables, the programmer attached to the crutches. The SUAW project, supported under BIOMED II Programme by the European Community was aimed to finalize and to put into practice the results of previous research and development. The novel implant with an ASCI-Chip has 16 channels, 8 on each side, 20 mA for monopolar and 2 mA for bipolar stimulation, only one electrode can be stimulated at a given time. Stimulation of 6 muscle groups of both legs are known to be sufficient for locomotion: M. ileopsoas (erector of the body, hip flexor), M. gluteus maximus (hip extensor), M. gluteus medius (lateral hip stabilisator, knee abductor), Mm. hamstrings (knee flexor) stimulated by epimysial electrodes, Mm. sartorius and rectus femoris (knee extensor) stimulated by neural, bipolar electrodes. Patient's selection criteria were: stable spinal cord lesion between T7 and T11, minimum 1 year after the accident without deformity of the spine, the muscle groups for locomotion responding to external FES with the EXOSTIM programmer with the same programme used later for the neuroprosthesis. Two paraplegic male patients, T8, 38 and 31 years old respectively, were operated on by an international group of surgeons according to the protocol in 09/1999, respectively 7/2000. The postop. course was uneventful. Because the threshold of the primary implant was too low regarding scare tissue around the electrodes, this implant was changed in 01/2000 and worked perfectly. Both patients are happy with the success of the novel treatment modalities.

Adult↗

Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle.

1. Ion-sensitive electrodes (made with a chloride-sensitive ion-exchange resin) were used to measure the internal chloride activity (a(i) (Cl)) of frog sartorius fibres at 25 degrees C.2. The internal pH (pH(i)) of other sartorius fibres was measured with a recessed tip pH-sensitive electrode (made with pH-sensitive glass).3. In normal bicarbonate-free solution (containing 2.5 mM potassium), the average chloride equilibrium potential, E(Cl) (calculated from a(i) (Cl) and the measured chloride activity of the external solution (a(o) (Cl)) was 87.7 +/- 1.7 mV (mean +/- S.E.; n = 16) in fibres where the average membrane potential, E(m), was 88.3 +/- 1.5 mV (mean +/- S.E.; n = 16). In experiments where a(i) (Cl) was varied between about 1 and 10 mM (which corresponds to values of E(m) between about -105 and -50 mV) E(Cl) was within 1-3 mV of E(m) at equilibrium. These measurements of a(i) (Cl) were obtained from the potential difference between the chloride-sensitive electrode and an intracellular indifferent micro-electrode filled with potassium chloride. If a potassium sulphate-filled indifferent micro-electrode was used, then values of a(i) (Cl) below about 5 mM were erroneously high, probably due to interference from other sarcoplasmic ions at the indifferent electrode.4. In solutions containing 15 mM bicarbonate and gassed with 5% CO(2), pH(i) was 6.9, corresponding to an internal bicarbonate concentration of 7.6 mM. E(Cl) measured in this solution was some 4 mV positive to E(m). Most of the difference between E(Cl) and E(m) could be ascribed to interference by sarcoplasmic bicarbonate on the basis of selectivity measurements of chloride against bicarbonate made on the ion-exchange resin in the relevant range of a(Cl).5. If bicarbonate/CO(2) in the external solution was replaced by HEPES/pure O(2) at constant pH, then pH(i) rose from 6.88 +/- 0.02 (mean +/- S.E.) to 7.05 +/- 0.02. A change in external pH of 1 unit caused pH(i) to change by about 0.02 unit and the intracellular buffering power was calculated to be about 35.6. In solution made hypertonic by the addition of sucrose, E(m) changed little or depolarized and E(Cl) and E(m) remained close. In contrast, in solution made hypertonic by the addition of solid sodium chloride (high-chloride solution) E(Cl) became negative to E(m). Conversely in low chloride solution E(Cl) became positive to E(m).7. When the chloride permeability (P(Cl)) was reduced by the use of acid solution, E(Cl) moved positive to E(m) indicating an accumulation of internal chloride. When P(Cl) was increased again by returning to more alkaline solution, E(m) depolarized to E(Cl).8. The results are consistent with the existence of a small, active movement of chloride, the effects of which are normally obscured by large passive movements of chloride when P(Cl) is large.

Animals↗

[Effect of low doses of sodium fluoride on the resistance of m. sartorius of frog to the injurious action of this substance].

A study was made of the effect of the preliminary maintenance of m. sartorius in 0.025 M NaF on their resistance to the injurious dose (0.12 M NaF). In the winter frogs, the muscle resistance to 0.12 M NaF increased statistically significant after 10 and 15 minutes maintenance in 0.25 M NaF by 27.8 and 34.6%, respectively. In spring frogs, the resistance increases as soon as after a 5 minutes preincubation by 22.5% (P less than 0.05). A 15 minutes incubation produced a similar effect as that observed in winter (32.8% P less than 0.05) A 15 minutes maintenance of muscles in a weak solution of NaF while increasing their resistance to the inhibitor was found to decrease their resistance to an injurious ethanol solution (3.48 M), and to 36 degrees, by 58 and 53%, respectively.

Animals↗