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M W Marshall

Publications and source records attributed to M W Marshall.

At least 19 recordsLinked to original sources
PubMed2006

Changes in intracellular pH play a secondary role in hydrogen sulfide-induced nasal cytotoxicity.

Hydrogen sulfide (H(2)S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is recognized as a public health concern. The nasal epithelium is particularly susceptible to H(2)S-induced pathology. Cytochrome oxidase inhibition is postulated as one mechanism of H(2)S toxicity. Another mechanism by which the weak acid H(2)S could cause nasal injury is intracellular acidification and cytotoxicity. To further understand the mechanism by which H(2)S damages the nasal epithelium, nasal respiratory and olfactory epithelial cell isolates and explants from naive rats were loaded with the pH-sensitive intracellular chromophore SNARF-1 and exposed to air or 10, 80, 200, or 400 ppm H(2)S for 90 min. Intracellular pH was measured using flow cytometry or confocal microscopy. Cell lysates were used to quantify total protein and cytochrome oxidase activity. A modest but statistically significant decrease in intracellular pH occurred following exposure of respiratory and olfactory epithelium to 400 ppm H(2)S. Decreased cytochrome oxidase activity was observed following exposure to >10 ppm H(2)S in both respiratory and olfactory epithelia. None of the treatments resulted in cytotoxicity. The intracellular acidification of nasal epithelial cells by high-dose H(2)S exposure and the inhibition of cytochrome oxidase at much lower H(2)S concentrations suggest that changes in intracellular pH play a secondary role in H(2)S-induced nasal injury.

Animals↗
PubMed2001

Influence of particle solubility on the delivery of inhaled manganese to the rat brain: manganese sulfate and manganese tetroxide pharmacokinetics following repeated (14-day) exposure.

Dissolution rate can influence the pulmonary clearance of a metal and thus affect its delivery to the brain and other organs. The goal of this study was to determine the exposure-response relationship for the relatively soluble sulfate (MnSO(4)) and insoluble tetroxide (Mn(3)O(4)) forms of inhaled manganese in adult male CD rats. Rats were exposed 6 h/day for 7 days/week (14 exposures) to either MnSO(4) or Mn(3)O(4) at 0, 0.03, 0.3, or 3 mg Mn/m(3). End-of-exposure olfactory bulb, striatum, cerebellum, bile, lung, liver, femur, serum, and testes (n = 6 rats/concentration/chemical) manganese concentrations and whole-body (54)Mn elimination were then determined. Increased whole-body (54)Mn clearance rates were observed in animals from the high-dose (3 mg Mn/m(3)) MnSO(4) and Mn(3)O(4) exposure groups. Elevated manganese concentrations in the lung were observed following MnSO(4) and Mn(3)O(4) exposure to > or=0.3 mg Mn/m(3). Increased olfactory bulb and femur manganese concentrations were also observed following MnSO(4) exposure at > or=0.3 mg Mn/m(3). Elevated striatal, testes, liver, and bile manganese concentrations were observed following exposure to MnSO(4) at 3 mg Mn/m(3). Elevated olfactory bulb, striatal, femur, and bile manganese concentrations were observed following exposure to Mn(3)O(4) at 3 mg Mn/m(3). Animals exposed to MnSO(4) (3 mg Mn/m(3)) had lower lung and higher olfactory bulb and striatal manganese concentrations compared with levels achieved following similar Mn(3)O(4) exposures. Our results suggest that inhalation exposure to soluble forms of manganese results in higher brain manganese concentrations than those achieved following exposure to an insoluble form of manganese.

Animals↗
PubMed2001

Neurotoxicological effects associated with short-term exposure of Sprague-Dawley rats to hydrogen sulfide.

Although hydrogen sulfide (H2S) is a known neurotoxic hazard, only a limited number of experimental animal studies have examined its neurochemical or behavioral effects. Our aim was to determine if short-term inhalation exposure of rats to H2S would result in altered brain catecholamnine levels or impaired learning and memory. Three groups of adult male CD rats were tested; two groups were exposed by nose-only inhalation (0, 30, 80, 200, or 400 ppm H2S) and one group was exposed by whole-body inhalation (0, 10, 30, or 80 ppm H2S) for 3 h per day forfive consecutive days. The first group (n = 10 rats per concentration) was tested immediately following each daily nose-only H2S exposure for spatial learning with a Morris water maze. Core body temperatures were also monitored in these animals during and after the last H2S exposure. The second group of rats (n = 10 rats per concentration) was tested for spontaneous motor activity immediately following the fifth exposure. These rats were then euthanized and striatal, hippocampal, and hindbrain catecholamnine levels determined. A third group of rats (n = 5-7 rats per concentration) was pretrained on a multiple fixed- interval (FI) schedule and exposed whole-body. Daily performance on the FI schedule was compared for the week pre-exposure, for the exposure week immediately following daily exposures, and for the week postexposure. We observed significant reductions in motor activity, water maze performance, and body temperature following exposure only to high concentrations (> or = 80 ppm) of H2S. Exposure to H2S did not affect regional brain catecholamine concentrations or performance on the FI schedule. Additional studies using other measures of behavior and longer-term exposure to H2S may be required to more definitively address conditions under which H2S exposure results in behavioral toxicity.

Administration, Inhalation↗
PubMed2001

Thrombosed hemodialysis grafts: lyse and wait with tissue plasminogen activator or urokinase compared to mechanical thrombolysis with the Arrow-Trerotola Percutaneous Thrombolytic Device.

PURPOSE: To determine if the lyse and wait (L&W) technique with a 4-mg dose of alteplase (tissue plasminogen activator; tPA) is a safe and effective method of declotting dialysis grafts as compared to use of the Arrow-Trerotola Percutaneous Thrombectomy Device (PTD) or the L&W technique with use of urokinase (UK). MATERIALS AND METHODS: Forty patients were randomized prospectively to undergo L&W declotting with use of 4 mg of tPA or mechanical thrombolysis with the PTD. The time interval to restored graft flow, total procedure time, hemostasis time, and anatomic success, clinical success, complications, and patency rates were analyzed. These were compared with historic results in 20 patients treated with the L&W technique with use of 250,000 U UK. RESULTS: The immediate anatomic success rate was 95% in the tPA L&W and PTD groups. The mean in-room lysis time with restored flow was 10 minutes for L&W with tPA and 19 minutes for PTD (P = .002). The mean in-room procedure time was 39 minutes for L&W and 45 minutes for PTD (P = NS). Mean hemostasis time with use of manual compression was 44 minutes for L&W with tPA and 23 minutes for PTD (P = .057). The historic group of 20 patients who underwent L&W with UK had a 95% anatomic success rate, a mean of 14 minutes of lysis time, a mean of 34 minutes of procedure time, and a mean of 26 minutes of time to hemostasis. No bleeding complications occurred in the PTD group. Seven episodes of bleeding occurred in six patients given tPA; four were delayed 60-90 minutes after the procedure, one necessitated hospitalization, and two required additional therapies. Four of the 20 patients undergoing L&W with UK had minor puncture site bleeding during the procedure. The 3-month primary patency rates were 65%, 65%, and 60% for L&W with tPA, PTD, and L&W with UK, respectively (P = NS). CONCLUSION: The 4-mg dose of tPA is effective but results in more bleeding complications and longer hemostasis times than mechanical thrombolysis with use of the PTD. Unlike in our experience with UK, bleeding complications with tPA were both major and delayed.

Blood Vessel Prosthesis↗
PubMed2001

Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats.

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.

Administration, Inhalation↗
PubMed2001

Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice.

Bromodichloromethane (BDCM) is a common municipal drinking water disinfection by-product, resulting in widespread trace human exposure via ingestion and inhalation. The present studies were designed to define organ-specific, BDCM-induced toxicity in wild type (p53(+/+)) and heterozygous (p53(+/-)) mice on both the FVB/N and C57BL/6 genetic backgrounds. Mice were exposed to BDCM vapor daily for 6 h/day and 7 days/week at concentrations of 0, 1, 10, 30, 100, or 150 ppm for 1 week and at 0, 0.3, 1, 3, 10, or 30 ppm for 3 weeks. In the 1-week exposure study, dose-dependent mortality and morbidity were observed at concentrations of 30 ppm and above and were as high as 100% at 150 ppm. In the 3-week exposure study, mortality and morbidity were found only in the 30-ppm exposure groups and were 0, 17, 67, and 33% for the wild-type C57BL/6, p53(+/-) C57BL/6, wild-type FVB/N, and p53(+/-) FVB/N mice, respectively. BDCM was a particularly potent kidney cytotoxicant. Dose-dependent tubular degeneration, necrosis, and associated regenerative cell proliferation greater than 10-fold over controls were seen at concentrations as low as 10 ppm in the kidneys of all strains at 1 week. Similar dose-dependent increases in hepatic necrosis, degeneration, and regenerative cell proliferation were observed but were induced only at concentrations of 30 ppm and higher. Pathological changes were more severe in the FVB/N compared to the C57BL/6 mice and were more severe in the heterozygotes compared to the wild-type mice. However, recovery and return of the percentage of kidney cells in S-phase to control levels was seen at 3 weeks. The estimated maximum tolerated dose for longer-term exposures was 15 ppm, based on mortality, induced kidney pathology, and regenerative cell proliferation. A one-year cancer bioassay was initiated with doses of 0, 0.5, 3, 10, and 15 ppm, based on this information. No pathological changes in the livers were found at the 13-week time point of that study. At 13 weeks, the kidney lesions and regenerative cell proliferation seen at the 1-week time point at doses of 10 ppm and above had resolved, and the cell proliferation rates had returned to baseline. Differences in toxicity indicate that caution be used in substituting wild-type mice for transgenic mice for range-finding studies to select doses for p53(+/-) cancer studies. Resolution of the kidney lesions indicates that periods of very high regenerative cell proliferation, potentially important in the carcinogenic process, may not be observed if measurements are taken only at 3 weeks of exposure or later.

Animals↗
PubMed1999

Using restorations borne totally by anterior implants to preserve the edentulous mandible.

BACKGROUND: This study quantifies the changes in bone height of the posterior area of the edentulous mandible when the load of complete dentures is borne entirely by anteriorly placed osseointegrated implants. METHODS: Thirty-three patients, of whom there were radiographs from the beginning of implant loading and from a follow-up visit at least three years later (a mean of 6.6 years later), were included in the study. Working with panoramic radiographs, the authors took height measurements in the premolar area (15 millimeters distal to the most distal implants). A valid correction factor was available because implants of known length were proximal to the area being evaluated. RESULTS: The authors calculated descriptive statistics using means, standard deviations, medians and proportions as appropriate. A P-value of less than .05 was considered significant. Of the 33 subjects, most showed increases in bone height--29 (87.9 percent) on the right side and 28 (84.9 percent) on the left side. The mean change in all subjects was +1.0 mm (range -0.8 to +3.3 mm). A comparison of mandibular height at implant placement vs. follow-up showed a statistically significant increase bilaterally (P < .001). CONCLUSIONS: This study demonstrates that dentures for edentulous mandibles that are borne totally by implants in the anterior area conserve or enhance the bone of the posterior portion of the mandible. An important future study should test the effect of implant-assisted restorations for the edentulous mandible that load the posterior ridge (a bar clasp, for example). CLINICAL IMPLICATIONS: One of the considerations in planning treatment for the edentulous mandible should be the preserving effect of totally implant-borne restorations vs. the continued resorption of the body of the mandible with conventional dentures.

Adult↗
PubMed1998

Surgical options for obstructive sleep apnea.

The pathology associated with obstructive sleep apnea is cumulative and progressive. When patients fail to improve with continuous nasal airway pressure or other, less-invasive treatments, surgery should be considered. The initial approach to the surgical patient is identification of all areas of potential obstruction. There are often several sites of obstruction, which can occur anywhere in the upper respiratory tract. One or more procedures may be needed to address these areas. The objective of surgery is to relieve these obstructing sites without interfering with the normal functionality of the upper airway.

Humans↗
PubMed1997

Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene.

1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5, 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene and styrene were genotoxic in mice, as shown by a significant increase in the frequency of micronucleated polychromatic erythrocytes. The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.

Animals↗
PubMed1992

The use of osseointegration to stabilize a surgical elongation of the maxilla: a case report.

Osseointegrated implants placed prior to maxillary downgrafting were utilized to stabilize the repositioned maxilla and interpositional bone graft. Eleven-month follow-up revealed complete healing of the 1.5-cm osteotomy gap and no maxillary relapse. Implant stabilization may be one solution to the relapse associated with inferior repositioning of the maxilla.

Dental Implantation, Endosseous↗
PubMed1991

Arthroscopic surgery for treatment of closed lock.

This study evaluates the first 51 consecutive cases treated for limitation of mandibular movement due to closed lock. Eighty joints (22 unilateral, 29 bilateral) were treated with arthroscopic surgery. The mean follow-up was 29.4 weeks, with a range of 6 to 77 weeks. These results showed an immediate improvement after arthroscopy followed by a more gradual improvement during the next 6 months, with a plateau in improvement thereafter. All cases, unilateral and bilateral, generally reached the same level of opening.

Adolescent↗
PubMed1991

Toxic interactions in the rat nose: pollutants from soiled bedding and methyl bromide.

Interactions between test chemicals and pollutants can confound toxicology studies. To test the sensitivity of the regenerating olfactory epithelium to additional challenge with the olfactory epithelial toxicant methyl bromide (MeBr), Fischer 344 (F344) rats received 2 6-hr inhalation exposures (separated by a 28-day recovery period) to either 0 or 175 ppm MeBr. The regenerating epithelium was resistant to the second MeBr exposure. In addition, histopathologic examination revealed squamous epithelial hyperplasia in the vestibule; inflammation, epithelial necrosis, mucosal erosions, and squamous metaplasia of the respiratory epithelium in the anterior nose; and olfactory sensory cell loss in the dorsal medial meatus. These changes could not be attributed to MeBr, but they were correlated with housing in filter-capped cages between MeBr exposures and were presumably caused by volatile pollutants from soiled bedding. Moreover, olfactory sensory cell loss in the dorsal medial meatus was associated with local resistance to MeBr-induced damage in rats with pollutant-induced changes. Analysis of cage air revealed a progressive increase in ammonia levels between bedding changes (up to 50 ppm), but exposure to 300 ppm ammonia in an additional experiment reproduced only the anterior nasal lesions and not olfactory sensory cell loss. This study demonstrates that 1) regenerating olfactory epithelium is refractory to further MeBr toxicity; 2) pollutants from soiled bedding (in addition to ammonia) produce nasal lesions; and 3) pollutant-induced changes modify the nasal response to inhaled MeBr.

Administration, Inhalation↗
PubMed1990

Excitation contraction coupling in normal and mdx mice.

The protein dystrophin is absent from patients with Duchenne muscular dystrophy and from the muscles of mdx mice. Recent studies have shown that dystrophin is located at the surface membrane and at the triadic junction, where it is associated with the transverse tubular membrane. Since the triadic junction is the site of excitation-contraction (EC) coupling, we have investigated whether intramembrane charge movement, a step in EC coupling, is modified by the absence of dystrophin. Charge movements are thought to arise from the transverse tubular membrane and to underlie the dependence of sarcoplasmic reticulum Ca2+ release on transverse tubular membrane potential. We find no differences between intramembrane charge movements or passive membrane electrical properties measured in muscles from mdx mice compared with normal mice. If dystrophin does play a role in EC coupling, that role is likely to be subsequent to the charge movement step.

Action Potentials↗
PubMed1990

Charge movements and transverse tubular ultrastructure in organ cultured skeletal muscle.

A study was made of charge movements and the transverse tubular systems in rat EDL and soleus muscle fibres maintained for up to five days in organ culture. In the cultured EDL muscle the maximum amount of charge moved was about one third of that in innervated muscle. Charge movements in innervated soleus fibres are small, less than 10 nC/microF, and difficult to resolve. They remain small following organ culturing. The ultrastructural study examined the concentration of junctional feet because of their proposed key role in excitation-contraction coupling. The general architecture of the triads and the spacing of the feet in both muscle types was largely unchanged by culturing. In cultured EDL muscles the small changes in feet concentration did not parallel the large fall in charge movement. The results reported here support a previous conclusion that, in mammalian muscle, there is not a simple relation between charge and feet. The stimulation of cultured soleus muscles with a fast twitch pattern of electrical activity produced no observable changes in morphology.

Animals↗
PubMed1990

The effects of tetracaine on charge movement in fast twitch rat skeletal muscle fibres.

1. The effects of tetracaine, a local anaesthetic that inhibits muscle contraction, on membrane potential and intramembrane charge movements were investigated in fast twitch rat muscle fibres (extensor digitorum longus). 2. The resting membrane potentials of surface fibres from muscles bathed in isotonic Ringer solution containing 2 mM-tetracaine were well maintained, but higher concentrations of tetracaine caused a time-dependent fall of potential. Muscle fibres bathed in hypertonic solutions containing 2 mM-tetracaine were rapidly depolarized. In both isotonic and hypertonic solutions, the depolarizing effect of tetracaine could not be reversed. 3. Charge movement measurements were made using the middle-of-the-fibre voltage clamp technique. The voltage dependence of charge movements measured in cold isotonic solutions was well fitted by a Boltzmann distribution (Q(V) = Qmax/(1 + exp(-(V-V)/k] where Qmax = 37.3 +/- 2.8 nC muF-1, V = -17.9 +/- 1.2 mV and k = 12.6 +/- 0.8 mV (n = 6, 2 degrees C; means +/- S.E. of means). Similar values were obtained when 2 mM-tetracaine was added to the isotonic bathing fluid (Qmax = 40.6 +/- 2.3 nC microF-1, V = -14.1 +/- 1.3 mV, k = 15.3 +/- 0.8 mV; n = 8, 2 degrees C). 4. Charge movements measured around mechanical threshold in muscle fibres bathed in hypertonic solutions were reduced when 2 mM-tetracaine was added to the bathing fluid. The tetracaine-sensitive component of charge was well fitted with an unconstrained Boltzmann distribution which gave: Qmax = 7.5 nC microF-1, V = -46.5 mV, k = 5.5 mV. The e-fold rise of the foot of the curve was 9.3 mV.

Action Potentials↗
PubMed1989

Relationship of dietary fat to plasma fatty acids, blood pressure, and urinary eicosanoids in adult men.

This experiment was conducted to determine the relationships between modest changes in dietary linoleate, blood pressure (BP) response, and levels of eicosanoid synthesis in humans. Products of eicosanoids which appear in blood were measured in urine: PGI2, 6-keto-PGF1 alpha (KPGI2); TXA2, (TXB2); PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha, (MPGF2 alpha). Twenty-three adult men were fed controlled diets having 25 energy percent fat, and having P/S ratios of either 0.3 (low-PUFA) or 1.0 (high-PUFA), for a total of 12 weeks, with a switchover between P/S ratios at 6 weeks. The results showed that, under the conditions of this study, BP was significantly reduced by reducing dietary fat intake from about 37 to 25 energy percent. However, no further effects on BP were produced by increasing the P/S ratio from 0.3 to 1.0. KPGI2 excretion was significantly lowered on both controlled diets as compared to the self-selected (SS) diet. However, MPGF2 alpha was lowered only on the low-PUFA diet as compared to the self-selected diet. No significant decrease in TXB2 excretion was observed. Both MPGF2 alpha and KPGI2 excretion were positively correlated with urine volume and sodium excretion. On the SS diet, but not on the controlled diets, MPGF2 alpha excretion was negatively correlated with plasma linoleate and positively correlated with stearate. On the low-PUFA diet, MPGF2 alpha excretion increased with the intake of linoleate, while, on the high-PUFA diet, it decreased. This may have been due to the limited amounts of linoleate available in the low-PUFA diet (3.2-3.4 energy percent) as compared to that in the high-PUFA diet. Both KPGI2 and MPGF2 alpha excretion were positively correlated with systolic and diastolic BP. These results suggest that the amount of dietary linoleate is an important factor in the regulation of prostaglandin synthesis in humans.

Adult↗
PubMed1989

Effects of intracellular ruthenium red on excitation-contraction coupling in intact frog skeletal muscle fibres.

1. Ruthenium Red (RR) blocks sarcoplasmic reticulum (SR) Ca2+ release in disrupted muscle preparations and this block has been used as a marker for the physiological Ca2+ release pathway. To investigate whether RR can also affect SR Ca2+ release in living muscle, optical signals reflecting Ca2+ release have been measured in intact single frog twitch fibres microinjected with RR. 2. The total myoplasmic concentration of RR, [RRT], was obtained from measurements of RR-related absorbance and apparent diffusion constant, Dapp, of RR in myoplasm was estimated. The value of Dapp was about 1/30 of that expected and can be explained if the majority of RR (approximately 97%) was bound in myoplasm and free [RR] was only 1/30 of [RRT]. 3. Sarcoplasmic reticulum Ca2+ release following action potential stimulation was assessed from a Ca2+-related change in intrinsic birefringence. The birefringence signal was blocked in the presence of RR and the degree of block was clearly dependent upon [RRT]. At 16 degrees C the estimated [RRT] for half-block of the birefringence signal was 23 +/- 4 microM (+/- S.E. of mean; n = 3), and for half-block of the Ca2+ release process itself was 72 +/- 14 microM. The estimated free [RR] for half-block is then 0.8 +/- 0.1 and 2.4 +/- 0.5 microM, respectively. In the cold (6-8 degrees C), the half-blocking concentration of RR, referred to [RRT], appeared to be about 3-fold smaller than that observed at 16 degrees C. 4. The values estimated for the free [RR] which caused half-block of Ca2+ release in intact muscle fibres are in the range reported for RR's action in disrupted preparations, thus supporting the conclusion that the RR-blockable channel observed in disrupted muscle is the physiologically important Ca2+ release channel. 5. Intramembrane charge movements in skeletal muscle are thought to underlie the dependence of SR Ca2+ release on transverse tubular membrane potential. Charge movements were measured in RR-injected fibres at 4-6 degrees C using a three-microelectrode, middle-of-the-fibre voltage-clamp technique. Injected fibres did not survive well in solutions made hypertonic to prevent fibre movement and allow measurement of suprathreshold charge; therefore charge movements below contraction threshold were studied in isotonic solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗