Search PubMed⌕ Search

Biomedical subjects

M J Kushmerick

Publications and source records attributed to M J Kushmerick.

At least 19 recordsLinked to original sources
PubMed1995

Creatine kinase equilibration follows solution thermodynamics in skeletal muscle. 31P NMR studies using creatine analogs.

The hypothesis tested was whether creatine kinase (CK) equilibrates with its substrates and products in the cytosol as if in solution. We used the creatine analogs cyclocreatine (cCr) or beta-guanidopropionate (beta GPA) to test if mass action ratios (gamma) for CK in muscle could be predicted from combined equilibrium constants (Kcomb) measured in solutions mimicking the intracellular environment. Mice were fed cCr or beta GPA and their muscles assayed for substrates and products of the CK reaction by 31P NMR spectroscopy and high performance liquid chromatography. After three weeks of feeding, gamma was indistinguishable from Kcomb in cCr-treated muscles demonstrating both PCr/Cr and phospho-analog/analog must have equilibrated with a constant and uniform cellular ATP/ADP ratio. In beta GPA-treated muscles, gamma was smaller than Kcomb due to a higher content of muscle beta GPA. Feeding beta GPA for 9-12 weeks resulted in a closer agreement between Kcomb and gamma, suggesting ATP/ADP ratios are not uniform within the muscle perhaps due to transient metabolic stress in some cells. From this analysis it follows that calculation of free ADP from the CK equilibrium for a heterogeneous population of cells with respect to total Cr and ATP content is correct only if chemical potentials of these cells are uniform.

Adenosine Diphosphate↗
PubMed1995

Effect of physiological ADP concentrations on contraction of single skinned fibers from rabbit fast and slow muscles.

To directly assess the possible role of ADP in muscle fatigue, we have studied the effect of physiological MgADP levels on maximum Ca(2+)-activated isometric force and unloaded shortening velocity (Vus) of single skinned fiber segments from rabbit fast-twitch (psoas) and slow-twitch (soleus) muscles. MgADP concentration was changed in a controlled and well-buffered manner by varying creatine (Cr) in solutions, which also contained MgATP, phosphocreatine (PCr), and creatine kinase (CK). To quantify ADP as a function of Cr added, we determined the apparent equilibrium constant (K') of CK for the conditions of our experiments (pH 7.1, 3 mM Mg2+, 12 degrees C): K' = (sigma [Cr]. sigma [ATP])/(sigma [PCr]. sigma [ADP]) = 260 +/- 3 (SE). In this manner, ADP was altered essentially as occurs during stimulation in vivo but without the concomitant changes in pH and P(i), which affect force and Vus. As ADP (and Cr) was increased, force and Vus decreased in both fiber types; at the highest ADP level used, 200 microM, normalized force was 96.6 +/- 1.7% for psoas (n = 6) and 93.7 +/- 2.8% for soleus (n = 6), and Vus was 80.4 +/- 2.4% for psoas and 91.3 +/- 7.7% for soleus. Diffusion-reaction calculations indicated that radial gradients of metabolite concentrations within fibers could not explain the small effects of ADP on fiber mechanics, and experiments verified that metabolite levels were well buffered within fibers by the CK reaction. Exogenous CK was added to bathing solutions at 290 U/ml, threefold above that necessary to maintain Vus independent of CK concentration; in the absence of PCr and exogenous CK, at least a fourfold increased MgATP was necessary to maintain Vus at the control level. Adenylate kinase activity was not detectable; thus myofibrillar adenosine-triphosphatase and exogenous CK activities were the major determinants of nucleotide levels within activated cells. Cr alone (in absence of PCr and exogenous CK) also decreased force and Vus, presumably by a nonspecific mechanism. Over the physiological range, altered ADP had little or no effect on force or Vus in well-buffered conditions. It is therefore likely that other factors decrease force and Vus during muscular fatigue.

Adenosine Diphosphate↗
PubMed1994

Simultaneous and separable flux of pathways for glucose and glycogen utilization studied by 13C-NMR.

Glucose utilization and glycogen turnover was studied by 13C-NMR in segments of hog carotid artery smooth muscle. After superfusion of carotid segments for 8-16 h at 37 degrees C with C-1 labeled glucose. 13C-NMR spectra revealed substantial incorporation into glycogen, lactate and into resonances tentatively identified as glutamate at the C-2 and C-4 positions. The rate of net glycogen incorporation was approximately linear over 8 h in unstimulated muscle. After washing out the initial labeled glucose, carotids were contracted by 80 mM KCl in the presence of C-2 labeled glucose. During the contraction simultaneous flux of glycogenolysis and glycolysis was observed with production of lactate labeled at the C-2 position (from glucose labeled at the second carbon) and with the magnitude of the glycogen resonance decreasing. However, no lactate labeled at the C-3 position (derived from C-3 glycogen) was observed at the end of a prolonged contraction. If complete mixing of the intermediates of the two pathways occurred, lactate derived from both glucose and glycogen would have been observed. When similar experiments are performed in the presence of 5 mM NaCN to block oxidative metabolism, then lactate derived from glucose and from glycogen was clearly observed. Therefore, when oxidative metabolism was intact, the intermediates of glycogenolysis and glycolysis did not normally appear to fully mix despite simultaneous flux of the two pathways during contraction. These separable cytosolic pathways for carbohydrate utilization are proposed to be governed by a reaction-diffusion class of mechanism. Such an organization of cytosolic enzymes may represent a general feature of cell metabolism.

Animals↗
PubMed1994

Activity of creatine kinase in a contracting mammalian muscle of uniform fiber type.

We investigated whether the creatine kinase-catalyzed phosphate exchange between PCr and gamma ATP in vivo equilibrated with cellular substrates and products as predicted by in vitro kinetic properties of the enzyme, or was a function of ATPase activity as predicted by obligatory "creatine phosphate shuttle" concepts. A transient NMR spin-transfer method was developed, tested, and applied to resting and stimulated ex vivo muscle, the soleus, which is a cellularly homogeneous slow-twitch mammalian muscle, to measure creatine kinase kinetics. The forward and reverse unidirectional CK fluxes were equal, being 1.6 mM.s-1 in unstimulated muscle at 22 degrees C, and 2.7 mM.s-1 at 30 degrees C. The CK fluxes did not differ during steady-state stimulation conditions giving a 10-fold range of ATPase rates in which the ATP/PCr ratio increased from approximately 0.3 to 1.6. The observed kinetic behavior of CK activity in the muscle was that expected from the enzyme in vitro in a homogeneous solution only if account was taken of inhibition by an anion-stabilized quaternary dead-end enzyme complex: E.Cr.MgADP.anion. The CK fluxes in soleus were not a function of ATPase activity as predicted by obligatory phosphocreatine shuttle models for cellular energetics.

Adenosine Triphosphatases↗
PubMed1994

Unloaded shortening of skinned muscle fibers from rabbit activated with and without Ca2+.

Unloaded shortening velocity (VUS) was determined by the slack method and measured at both maximal and submaximal levels of activation in glycerinated fibers from rabbit psoas muscle. Graded activation was achieved by two methods. First, [Ca2+] was varied in fibers with endogenous skeletal troponin C (sTnC) and after replacement of endogenous TnC with either purified cardiac troponin C (cTnC) or sTnC. Alternatively, fibers were either partially or fully reconstituted with a modified form of cTnC (aTnC) that enables force generation and shortening in the absence of Ca2+. Uniformity of the distribution of reconstituted TnC across the fiber radius was evaluated using fluorescently labeled sTnC and laser scanning fluorescence confocal microscopy. Fiber shortening was nonlinear under all conditions tested and was characterized by an early rapid phase (VE) followed by a slower late phase (VL). In fibers with endogenous sTnC, both VE and VL varied with [Ca2+], but VE was less affected than VL. Similar results were obtained after extraction of TnC and reconstitution with either sTnC or cTnC, except for a small increase in the apparent activation dependence of VE. Partial activation with aTnC was obtained by fully extracting endogenous sTnC followed by reconstitution with a mixture of aTnC and cTnC (aTnC:cTnC molar ratio 1:8.5). At pCa 9.2, VE and VL were similar to those obtained in fibers reconstituted with sTnC or cTnC at equivalent force levels. In these fibers, which contained aTnC and cTnC, VE and VL increased with isometric force when [Ca2+] was increased from pCa 9.2 to 4.0. Fibers that contained a mixture of a TnC and cTnC were then extracted a second time to selectively remove cTnC. In fibers containing aTnC only, VE and VL were proportional to the resulting submaximal isometric force compared with maximum Ca(2+)-activated control. With aTnC alone, force, VE, and VL were not affected by changes in [Ca2+]. The similarity of activation dependence of VUS whether fibers were activated in a Ca(2+)-sensitive or -insensitive manners implies that VUS is determined by the average level of thin filament activation and that, with sTnC or cTnC, VUS is affected by Ca2+ binding to TnC only.

Animals↗
PubMed1994

Contractile economy and aerobic recovery metabolism in skeletal muscle adapted to creatine depletion.

Mice were treated for 7-12 wk with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Treatment reduced total creatine to approximately 5% of control values in soleus (SOL) and extensor digitorum longus (EDL) muscles. In both muscles from treated mice, phosphorylated beta-GPA accumulated and resting [ATP] decreased by approximately 50%. Relative to controls, cytochrome oxidase and citrate synthase activities increased significantly in EDL from treated mice, but not in SOL; creatine kinase activity decreased significantly in SOL, but not in EDL. Measurements of poststimulation energy metabolism show that the energy cost to maintain tension in SOL and EDL from treated mice was approximately 50% of that in control muscle. Relative to controls, first-order rate constants of poststimulation O2 demand were 2- and 3.6-fold greater in SOL and EDL, respectively, from treated mice. Increased economy of SOL and EDL from treated mice is consistent with previously reported changes in myosin isoenzymes. Increases in rate constants of O2 utilization in creatine-depleted muscle are inconsistent with the hypothesis that cytoplasmic or mitochondrial creatine kinase is rate limiting for cellular respiration.

Adaptation, Physiological↗
PubMed1994

Relationship between intracellular pH, extracellular pH, and ventilation during dilution acidosis.

Previous experiments showed that acute hyperosmolality results in an extracellular acidosis that does not stimulate respiratory compensation (C.E. Kasserra, D. R. Jones, and M. R. Hughes. Respir. Physiol. 85: 383-393, 1991). The data suggested that development of the extracellular dilution acidosis would also result in a concomitant intracellular contraction alkalosis. The effects of acute hyperosmolality and lactacidosis on systemic intracellular pH (pHi) were studied in the conscious Pekin duck in an effort to separate the effects of pHi and extracellular pH (pHe) on ventilatory control. Brain pH was also measured during systemic hyperosmolality to determine the relationship between blood and brain pHi. Hyperosmolality caused a concurrent extracellular acidosis and intracellular alkalosis in pectoral muscle, whereas lactic acid infusion decreased both pHe and pHi. Ventilation was stimulated only during lactacidosis and did not change during hyperosmolality. Brain pHi did not show a consistent significant increase in response to systemic hyperosmolality over 1 h but did show a trend toward an alkalosis. Measurement of high-energy phosphate metabolites (phosphocreatine, ATP, and Pi) indicated an increase of metabolic rate during hyperosmolality. With the assumption that similar pHi changes were occurring in chemoreceptive cells, the results suggest that ventilation was responding to pHi changes and that much of the depressive response to acute hyperosmotic disturbance was peripherally generated.

Acidosis, Lactic↗
PubMed1993

Two classes of mammalian skeletal muscle fibers distinguished by metabolite content.

Phosphorus NMR spectroscopy and HPLC analyses were made on isolated rat and mouse muscles selected for different volume fractions of the major known fiber types. We tested the hypothesis that muscle cell types at rest have intrinsically different contents of PCr, ATP and Pi. The Pi content was low and the PCr and ATP contents were high in muscles with large contents of type 2b and 2a fibers, and vice versa in muscles with large volume fraction of types 1 and 2x fibers. From the profile of these metabolites we could distinguish only two classes of fibers in the murine muscles and predict well the composition of cat muscles. For the first class, types 2a and 2b fibers, the intracellular concentrations were: ATP 8 mM; total Cr 39 mM; PCr 32 mM; Pi 0.8 mM; ADP 8 microM. For the second class, type 1 and 2x fibers, these quantities are: ATP 5 mM; TCr 23 mM; PCr 16 mM; Pi 6 mM; ADP 11 microM. Thus our results establish a new and apparently general criterion upon which to distinguish skeletal muscle cells, one based on the resting content of bioenergetically important metabolites.

Animals↗
PubMed1993

Separate measures of ATP utilization and recovery in human skeletal muscle.

1. The chemical changes during contractile activity were separated from recovery metabolism in the forearm flexor musculature in normal human subjects using 31P nuclear magnetic resonance (NMR) spectroscopy. Percutaneous, supramaximal twitch stimulation of the median and ulnar nerves was used in combination with temporary ischaemia of the forearm to characterize the summed ATPase activity. The recovery following restoration of blood flow provided a measure of oxidative ATP synthesis activity. These processes were measured based on the dynamics of creatine phosphate (PCr) content. 2. Muscle oxygen stores were depleted using ischaemia without stimulation as indicated by PCr breakdown after 250 +/- 33 s (mean +/- S.D.; n = 5), which provided a measure of the basal metabolic rate (0.008 +/- 0.002 mM s-1, n = 5). 3. The PCr breakdown rate during twitch stimulation of the oxygen-depleted muscle was constant at 1 Hz at 0.15 +/- 0.03 mM PCr per second or per twitch (n = 8). A constant cost per twitch was found from 0.5 to 2 Hz stimulation (depletion of PCr per twitch = 0.15 mM per twitch). 4. No net anaerobic recovery of PCr was found during a 2 min post-stimulation ischaemia. 5. Upon restoration of blood flow, PCr recovery followed an exponential time course with a time constant of 63 +/- 14 s (n = 8). From these recovery rates, the capacity for oxidative phosphorylation was estimated to be 0.4 mM s-1. 6. This experimental approach defines a non-invasive and quantitative measure of human muscle ATPase rate and ATP synthetase rate.

Adenosine Triphosphatases↗
PubMed1992

Antibody and peptide probes of interactions between the SH1-SH2 region of myosin subfragment 1 and actin's N-terminus.

The negatively charged residues in the N-terminus of actin and the 697-707 region on myosin subfragment 1 (S-1), containing the reactive cysteines SH1 and SH2, are known to be important for actin-activated myosin ATPase activity. The relationship between these two sites was first examined by monitoring the rates of SH1 and SH2 modification with N-ethylmaleimide in the presence of actin and, secondly, by testing for direct binding of SH1 peptides to the N-terminal segment on actin. While actin alone protected SH1 from N-ethylmaleimide modification, this effect was abolished by an antibody against the seven N-terminal amino acids on actin, F(ab)(1-7), and was greatly reduced when the charge of acidic residues at actin's N-terminus was altered by carbodiimide coupling of ethylenediamine. Neither F(ab)(1-7) nor ethylenediamine treatment reversed the effect of F-actin on SH2 reactivity in SH1-modified S-1. These results show a communication between the SH1 region on S-1 and actin's N-terminus in the acto-S-1 complex. To test whether such a communication involves the binding of the SH1 site on S-1 to the N-terminal segment of actin, the SH1 peptide IRICRKG-NH2(4+) was used. Cosedimentation experiments revealed the binding of three to six peptides per actin monomer. Peptide binding to actin was affected slightly, if at all, by F(ab)(1-7). The antibody also did not change the polymerization of G-actin by the peptides. The peptides caused a small reduction in the binding of S-1 to actin and did not change the binding of F(ab)(1-7).(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1992

Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi.

We tested the proposition that muscle cell types have different contents of phosphocreatine (PCr), ATP, and Pi by 31P NMR spectroscopy and HPLC analyses of adult rat and mouse muscles containing various volume fractions of different fiber types. There was a 2-fold difference in the PCr content between muscles with a high volume fraction of fiber types 1 and 2x versus those with fast-twitch (types 2a and 2b) fiber types. Pi content was low, and PCr and ATP contents were high in muscles with large contents of type 2b and 2a fibers; the reverse was true in muscles with a large volume fraction of type 1 and 2x fibers. There is a large range in the Pi/PCr ratios in normal resting muscles, from less than 0.05 in type 2 to 0.51 in type 1 fibers, depending upon the distribution of their component fiber types. In all muscles, the peak area resulting from the beta phosphate of ATP constituted approximately 13% of the sum of all peak areas observable in the 31P spectrum. Fiber types 2a and 2b were not distinguishable, and the content of type 2x fibers was similar to type 1 fibers. From the profile of these metabolites, we could distinguish only two classes of fibers. For type 2a and 2b fibers, the intracellular concentrations were 8 mM ATP, 39 mM total creatine, 32 mM PCr, 0.8 mM Pi, and 8 microM ADP. For type 1 and 2x fibers, these quantities were 5 mM ATP, 23 mM total creatine, 16 mM PCr, 6 mM Pi, and 11 microM ADP. Thus our results establish an additional criterion upon which to distinguish skeletal muscle cells, one based on the resting content of bioenergetically important metabolites. These results also provide the basis for estimating skeletal muscle fiber-type composition from noninvasive NMR spectroscopic data.

Adenosine Triphosphate↗
PubMed1992

High-performance liquid chromatographic assays for free and phosphorylated derivatives of the creatine analogues beta-guanidopropionic acid and 1-carboxy-methyl-2-iminoimidazolidine (cyclocreatine).

Creatine and phosphocreatine are substrates for creatine kinase which is a key enzyme involved in energy transfer within the cell. Analogues of creatine have been fed to animals to determine the role this enzyme plays in energy metabolism, but progress in interpretation has been hampered by the lack of quantitative techniques to determine tissue content of these compounds. We describe the separation and quantitation of substituted guanidino compounds and their phosphorylated forms by high-performance liquid chromatography. First, a cation-exchange column is used to assay free creatine and its unphosphorylated analogues, and then phosphocreatine and its phosphorylated analogues as well as adenylate content (AMP, ADP, ATP) are assayed on an anion-exchange column. These methods have proven successful in measuring the chemical contents of these compounds in neutralized perchloric acid extracts of mammalian skeletal muscles. The sensitivity of this method ranges from 50 to 200 pmol, which is adequate to provide information from tissue extracts of 5- to 10-mg samples.

Animals↗
PubMed1992

Vascular oxidative metabolism under different metabolic conditions.

Control of respiration in vascular smooth muscle was examined while the metabolic state of the tissue was manipulated. During KCl-induced contractures in the presence of 5 mM glucose, oxygen consumption increased by 10 nmol/per min g without any decrease in phosphocreatine (PCr) or ATP as determined by 31P-NMR indicating a control of respiration which does not involve changes in high-energy phosphates (e.g., ADP, phosphorylation potential). However, when aortae with resting tone in the absence of substrate were then provided with 5 mM 2-deoxyglucose as the sole substrate, oxygen consumption increased 7.4 nmol/min per g while PCr decreased by more than 50% (resulting in a 2-fold increase in the calculated free ADP) with no change in tension from resting tone. During a subsequent KCl induced contracture in the presence of 2-deoxyglucose, oxygen consumption increased an additional 7.2 nmol/min per g while PCr continued to decline. Therefore, at least two mechanisms of respiratory control may exist in sheep aorta, one dependent and the other independent of changes in high-energy phosphates.

Adenosine Diphosphate↗
PubMed1992

Tension responses of sheep aorta to simultaneous decreases in phosphocreatine, inorganic phosphate and ATP.

1. Tension responses of sheep aortae were investigated when different substrates were included in the superfusing medium. The magnitude of tension development was similar whether or not 5 mM glucose was present in the medium. However, the rate of tension development was greater in the absence of glucose. 2. When 5 mM 2-deoxyglucose (2DG) was present in the medium, the magnitude of tension generation was 1.6 times that in the absence of exogenous substrate. A second sequential contraction with 2DG generated tension 1.25 times that in the absence of exogenous substrate. The rate of tension development during the first contraction in the presence of 2DG was similar to that in the absence of substrate. However, the second contraction in the presence of 2DG had a substantially increased rate of tension development. 3. 31P nuclear magnetic resonance (NMR) spectroscopy revealed that, at resting tone, in the presence of 2DG, inorganic phosphate (P(i)) and phosphocreatine (PCr) simultaneously decrease while 2-deoxyglucose-6-phosphate accumulates. During contraction-relaxation cycles, in the presence of 2DG, P(i) and PCr become undetectable while ATP declines to approximately 50% of control values as determined by NMR. During the second contraction in the presence of 2DG, the area of the ADP resonance was similar to that of the alpha-ATP resonance. 4. The increase in the magnitude of tension generation, during 2DG administration, correlated with a decrease in P(i) levels. The rate of relaxation from a contraction, in the presence of 2DG, was slower than in the presence of glucose or in the absence of exogenous substrate. These results are consistent with the role of P(i) in the release of the proposed 'latch-bridge' state of maintained contraction at low energy demand. 5. The increase in isometric tension generation during contraction in the presence of 2DG appears to be related to the decreased levels of P(i). In the presence of 2DG, the reduction of PCr and of ATP occur to a similar extent to that during hypoxia, yet no inhibition of force takes place. The low levels of ATP and PCr reported with 2DG administration in these studies do not energetically limit the contractile apparatus.

Adenosine Triphosphate↗
PubMed1992

Regulation of oxygen consumption in fast- and slow-twitch muscle.

Phosphorus nuclear magnetic resonance spectra and steady-state O2 consumption rates were obtained from ex vivo arterially perfused cat biceps brachii (fast twitch) and soleus (slow twitch) muscles during and after periods of isometric twitch stimulation at 30 degrees C. In the biceps muscles, steady-state O2 consumption increased and phosphocreatine (PCr) concentration decreased progressively with stimulation. PCr recovery after these stimulation periods followed first-order kinetics with a half time of 10 min. The results in the biceps could be explained by a feedback control of cellular respiration by ADP concentration. In the soleus, steady-state O2 consumption also increased and PCr concentration decreased as stimulation rates increased. The half time for PCr recovery in the soleus was approximately 5 min, but, in contrast to the pattern in the biceps, the kinetics was not first order. There was an overshoot during the recovery period in the PCr content of soleus and a corresponding undershoot of Pi compared with resting values. Mitochondrial regulation by ADP is not sufficient to account for respiratory control in slow-twitch soleus. The respiration rate in neither muscle was dependent on the Pi content. Thus we conclude that the mechanism of control of cellular respiration is both quantitatively and qualitatively different in fast- and slow-twitch skeletal muscle.

Adenosine Diphosphate↗
PubMed1991

Molecular charge dominates the inhibition of actomyosin in skinned muscle fibers by SH1 peptides.

It is not definitively known whether the highly conserved region of myosin heavy chain around SH1 (Cys 707) is part of the actin-binding site. We tested this possibility by assaying for competitive inhibition of maximum Ca-activated force production of skinned muscle fibers by synthetic peptides which had sequences derived from the SH1 region of myosin. Force was inhibited by a heptapeptide (IRICRKG) with an apparent K0.5 of about 4 mM. Unloaded shortening velocity of fibers, determined by the slack test, and maximum Ca-activated myofibrillar MgATPase activity were also inhibited by this peptide, but both required higher concentrations. We found that other cationic peptides also inhibited force in a manner that depended on the charge of the peptide; increasing the net positive charge of the peptide increased its efficacy. The inhibition was not significantly affected by altering solution ionic strength (100-200 mM). Disulfide bond formation was not involved in the inhibitory mechanism because a peptide with Thr substituted for Cys was inhibitory in the presence or absence of DTT. Our data demonstrate that the net charge was the predominant molecular characteristic correlated with the ability of peptides from this region of myosin heavy chain to inhibit force production. Thus, the hypothesis that the SH1 region of myosin is an essential part of the force-producing interaction with actin during the cross-bridge cycle (Eto, M., R. Suzuki, F. Morita, H. Kuwayama, N. Nishi, and S. Tokura., 1990, J. Biochem. 108:499-504; Keane et al., 1990, Nature (Lond.). 344:265-268) is not supported.

Actomyosin↗
PubMed1991

Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle.

Phosphocreatine (PCr) and intracellular pH changes were monitored by 31P-NMR spectroscopy in isolated, arterially perfused cat biceps and soleus muscles, while the pH of the CO2-bicarbonate buffered perfusate was decreased from 7.1-7.4 to 6.4-6.7 by increasing the CO2 in the equilibrating gas from 5 to up to 70%. In biceps (fast twitch) muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force decreased by 8%, but the rise and relaxation times of tetanic were not significantly changed. In soleus muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force was unchanged, but the rise and relaxation times of tetani were increased by 27 and 112%, respectively. In both muscles greater decreases in tetanic force were observed during repetitive or ischemic stimulation, which resulted in intracellular pH similar to that produced by hypercapnia. Contrary to previous reports, there was no significant decrease in PCr level in either muscle type with decreased intracellular pH. In the soleus at 30 degrees C there was a significant increase in PCr level with decreased pH.

Animals↗