Biomedical subjects

S E Gordon

Publications and source records attributed to S E Gordon.

At least 37 records · Page 2Linked to original sources

PubMed1999

Stoichiometry and arrangement of subunits in rod cyclic nucleotide-gated channels.

Cyclic nucleotide-gated (CNG) ion channels mediate the response to light in retinal rods. They are tetramers of two homologous subunits (alpha and beta), each of which is essential for the function of the channels in vivo. We have investigated the stoichiometry and arrangement of these two subunits to determine how they come together within an individual channel complex. We exploited the very specific geometric and spatial requirements for forming a high-affinity Ni2+-binding site to examine the number and relative positions of the subunits. We found that only an order of alpha/alpha/beta/beta could account qualitatively and quantitatively for the observed intersubunit coordination of Ni2+ in wild-type and mutant alpha/beta channels. Furthermore, our results suggest a structural dimerization among like subunits, at least at the level of the Ni2+-binding site.

Amino Acid Sequence↗

PubMed1999

Influence of exercise training on physiological and performance changes with weight loss in men.

PURPOSE: The purpose of this study was to examine the physiological effects of a weight-loss dietary regimen with or without exercise. METHODS: Thirty-five overweight men were matched and randomly placed into either a control group (C; N = 6) or one of three dietary groups; a diet-only group (D; N = 8), a diet group that performed aerobic exercise three times per week (DE; N = 11); and a diet group that performed both aerobic and strength training three times per week (DES; N = 10). RESULTS: After 12 wk, D, DE, and DES demonstrated a similar and significant (P < or = 0.05) reduction in body mass (-9.64, -8.99, and -9.90 kg, respectively) with fat mass comprising 69, 78, and 97% of the total loss in body mass, respectively. The diet-only group also demonstrated a significant reduction in fat-free mass. Maximum strength, as determined by 1-RM testing in the bench press and squat exercise was significantly increased for DES in both the bench press (+19.6%) and squat exercise (+32.6%). Absolute peak O2 consumption was significantly elevated in DE (+24.8%) and DES (+15.4%). There were no differences in performance during a 30-s Wingate test for the DE and DES, whereas D demonstrated a significant decline in peak and mean power output. Resting metabolic rate (RMR) (kcal x d(-1)) was not significantly different for any of the groups except for the DE group. There were no significant changes in basal concentrations of serum glucose, BUN, cortisol, testosterone, and high density lipoprotein (HDL) cholesterol for any of the groups. Serum total cholesterol and low density lipoprotein (LDL) cholesterol were significantly decreased for all dietary groups. Serum triglycerides were significantly reduced for D and DES at week 6 and remained lower at week 12 for D, while triglycerides returned to baseline values for DES. CONCLUSIONS: These data indicate that a weight-loss dietary regimen in conjunction with aerobic and resistance exercise prevents the normal decline in fat-free mass and muscular power and augments body composition, maximal strength, and maximum oxygen consumption compared with weight-loss induced by diet alone.

Adult↗

PubMed1999

Acute hormonal responses to a single bout of heavy resistance exercise in trained power lifters and untrained men.

The purpose of this study was to investigate the acute responses of both stress and fluid regulatory hormones to a single bout of resistance exercise in both trained and untrained men. Seven competitive power lifters (PL) and 12 untrained subjects (UT) performed one set of the leg press exercise to exhaustion at 80% of their respective one-repetition maximum. Blood samples were obtained twice prior to exercise (at P1 and P2), immediately postexercise (IP), and at 5 minutes postexercise (5PE). Compared to P1 and P2, plasma epinephrine, norepinephrine, dopamine, atrial peptide, osmolality, and blood lactic acid increased significantly (p < or = 0.05) at IP. Plasma epinephrine, norepinephrine, atrial peptide, and blood lactic acid concentrations remained elevated at 5PE compared to P1 and P2. Plasma renin activity and angiotensin II were significantly elevated at 5PE compared to P1, P2, and IP, and this increase was significantly greater in PL compared to UT at 5PE. These data indicate that an acute bout of resistance exercise dramatically affects secretion of stress and fluid regulatory hormones.

Adrenergic alpha-Agonists↗

PubMed1999

Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle.

Components of signaling pathways for mechanotransduction during load-induced enlargement of skeletal muscle have not been completely defined. We hypothesized that loading of skeletal muscle would result in an adaptive increase in the expression of two focal adhesion complex (FAC)-related proteins, focal adhesion kinase (FAK) and paxillin, as well as increased FAK activity. FAK protein was immunolocalized to the sarcolemmal region of rooster anterior latissimus dorsi (ALD) myofibers in the middle of the ALD muscle. FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Western blots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle. FAK autokinase activity in immunoprecipitates was increased after 1.5, 7, and 13 days in stretched ALD muscles. To determine whether increased FAK and paxillin protein concentrations are associated with hypertrophy and/or new fiber formation, two additional experiments were performed. First, during formation of primary chicken myotubes (a model of new fiber formation), FAK protein concentration (63%), FAK activity (157%), and paxillin protein concentration (97%) increased compared with myoblasts. Second, FAK (112% and 611%) and paxillin (87% and 431%) protein concentrations per unit of total protein in the soleus muscle increased at 1 and 8 days after surgical ablation of the synergistic gastrocnemius muscle (a model of hypertrophy without hyperplasia). Thus increases in components of the FAC occur in hypertrophying muscle of animals and in newly formed muscle fibers in culture. Furthermore, increased FAK activity suggests a possible convergence of signaling at the FAC in load-induced growth of skeletal muscle.

Animals↗

PubMed1999

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading.

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

Animals↗

PubMed1999

Effects of heavy-resistance training on hormonal response patterns in younger vs. older men.

To examine the adaptations of the endocrine system to heavy-resistance training in younger vs. older men, two groups of men (30 and 62 yr old) participated in a 10-wk periodized strength-power training program. Blood was obtained before, immediately after, and 5, 15, and 30 min after exercise at rest before and after training and at rest at -3, 0, 6, and 10 wk for analysis of total testosterone, free testosterone, cortisol, growth hormone, lactate, and ACTH analysis. Resting values for insulin-like growth factor (IGF)-I and IGF-binding protein-3 were determined before and after training. A heavy-resistance exercise test was used to evaluate the exercise-induced responses (4 sets of 10-repetition maximum squats with 90 s of rest between sets). Squat strength and thigh muscle cross-sectional area increased for both groups. The younger group demonstrated higher total and free testosterone and IGF-I than the older men, training-induced increases in free testosterone at rest and with exercise, and increases in resting IGF-binding protein-3. With training the older group demonstrated a significant increase in total testosterone in response to exercise stress along with significant decreases in resting cortisol. These data indicate that older men do respond with an enhanced hormonal profile in the early phase of a resistance training program, but the response is different from that of younger men.

Adrenocorticotropic Hormone↗

PubMed1999

Zinc bioavailability in young adult rats fed sweet potato greens containing phytic acid.

This study determined whether phytic acid in sweet potato greens influences the bioavailability of zinc in young adult rats used as models for adult humans. A control diet (AIN-93M), two AIN-93M diets with pure phytic acid (PA) at 0.2% or 0.4%, and four diets with Georgia Jet or TU-82-155 dried blanched greens at 7.5% or 15% were fed to seven groups of 7-week male Harlan-Sprague rats for 21 days. Weight gains were generally not affected by PA concentration, were lower in the rats fed with sweet potato greens than in the control rats, and were similar in the rats fed with pure PA or control diet. Feed intake utilization, as indicated by the total weight gain per total feed intake, was almost similar in the different rat groups. Bone (femur, tibia) and organ (kidney, liver, lung, spleen) weights, except the heart weights, were similar for all diet groups. Their zinc concentrations were generally not affected by PA concentration but depended on the PA source.

Animal Feed↗

PubMed1998

Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days.

The effects of two different duration space-flights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight.

Animals↗

PubMed1998

Acute hormonal responses to heavy resistance exercise in younger and older men.

The purpose of this investigation was to examine the acute responses of several hormones [total and free testosterone (TT and FT, respectively), adrenocorticotropic hormone (ACTH), cortisol (C), growth hormone (GH), and insulin (INS)] to a single bout of heavy resistance exercise (HRE). Eight younger [30-year (30y) group] and nine older [62-year (62y) group] men matched for general physical characteristics and activity levels performed four sets of ten repetitions maximum (RM) squats with 90 s rest between sets. Blood samples were obtained from each subject via an indwelling cannula with a saline lock pre-exercise, immediately post-exercise (IP), and 5, 15 and 30 min post-exercise. Levels of TT, FT, ACTH, C and lactate significantly increased after HRE for both groups. Pre-HRE pairwise differences between groups were noted only for FT, while post-HRE pairwise differences were found for TT, FT, GH, glucose and lactate. Area under the curve analysis showed that the 30y group had a significantly higher magnitude of increase over the entire recovery period (IP, 5, 15, and 30 min post-exercise) for TT, FT, ACTH and GH. Few changes occurred in the INS response with the only change being that the 62y group demonstrated a decrease IP. Lactate remained elevated at 30 min post-HRE. This investigation demonstrates that age-related differences occur in the endocrine response to HRE, and the most striking changes appear evident in the FT response to HRE in physically active young and older men.

Adrenocorticotropic Hormone↗

PubMed1998

The effects of short-term resistance training on endocrine function in men and women.

This investigation examined hormonal adaptations to acute resistance exercise and determined whether training adaptations are observed within an 8-week period in untrained men and women. The protocol consisted of a 1-week pre-conditioning orientation phase followed by 8 weeks of heavy resistance training. Three lower-limb exercises for the quadriceps femoris muscle group (squat, leg press, knee extension) were performed twice a week (Monday and Friday) with every other Wednesday used for maximal dynamic 1 RM strength testing. Blood samples were obtained pre-exercise (Pre-Ex), immediately post-exercise (IP), and 5 min post-exercise (5-P) during the first week of training (T-1), after 6 weeks (T-2) and 8 weeks (T-3) of training to determine blood concentrations of whole-blood lactate (LAC), serum total testosterone (TT), sex-hormone binding globulin (SHBG), cortisol (CORT) and growth hormone (GH). Serum TT concentrations were significantly (P < or = 0.05) higher for men at all time points measured. Men did not demonstrate an increase due to exercise until T-2. An increase in pre-exercise concentrations of TT were observed both for men and women at T-2 and T-3. No differences were observed for CORT between men and women; increases in CORT above pre-exercise values were observed for men at all training phases and at T-2 and T-3 for women. A reduction in CORT concentrations at rest was observed both in men and women at T-3. Women demonstrated higher pre-exercise GH values than men at all training phases; no changes with training were observed for GH concentrations. Exercise-induced increases in GH above pre-exercise values were observed at all phases of training. Women demonstrated higher serum concentrations of SHBG at all time points. No exercise-induced increases were observed in men over the training period but women increased SHBG with exercise at T-3. SHBG concentrations in women were also significantly higher at T-2 and T-3 when compared to T-1 values. Increases in LAC concentrations due to exercise were observed both for men and women for all training phases but no significant differences were observed with training. These data illustrate that untrained individuals may exhibit early-phase endocrine adaptations during a resistance training program. These hormonal adaptations may influence and help to mediate other adaptations in the nervous system and muscle fibers, which have been shown to be very responsive in the early phase of strength adaptations with resistance training.

Adult↗

PubMed1998

Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men.

Effects of a 10-week progressive strength training program composed of a mixture of exercises for increasing muscle mass, maximal peak force, and explosive strength (rapid force production) were examined in 8 young (YM) (29+/-5 yrs) and 10 old (OM) (61+/-4 yrs) men. Electromyographic activity, maximal bilateral isometric peak force, and maximal rate of force development (RFD) of the knee extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF), muscle fiber proportion, and fiber areas of types I, IIa, IIb, and IIab of the vastus lateralis were evaluated. Maximal and explosive strength values remained unaltered in both groups during a 3-week control period with no training preceding the strength training. After the 10-week training period, maximal isometric peak force increased from 1311+/-123 N by 15.6% (p <.05) in YM and from 976+/-168 N by 16.5% (p <.01) in OM. The pretraining RFD values of 4049+/-791 N*s(-1) in YM and 2526+/-1197 N*s(-1) in OM remained unaltered. Both groups showed significant increases (p < .05) in the averaged maximum IEMGs of the vastus muscles. The CSA of the QF increased from 90.3+/-7.9 cm2 in YM by 12.2% (p <.05) and from 74.7+/-7.8 cm2 in OM by 8.5% (p <.001). No changes occurred in the muscle fiber distribution of type I during the training, whereas the proportion of subtype IIab increased from 2% to 6% (p < .05) in YM and that of type IIb decreased in both YM from 25% to 16% (p < .01) and in OM from 15% to 6% (p < .05). The mean fiber area of type I increased after the 10-week training in YM (p < .001) and OM (p < .05) as well as that of type IIa in both YM (p < .01) and OM (p < .01). The individual percentage values for type I fibers were inversely correlated with the individual changes recorded during the training in the muscle CSA of the QF (r=-.56, p < .05). The present results suggest that both neural adaptations and the capacity of the skeletal muscle to undergo training-induced hypertrophy even in older people explain the gains observed in maximal force in older men, while rapid force production capacity recorded during the isometric knee extension action remained unaltered during the present mixed strength training program.

Adult↗

PubMed1998

Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy.

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

Actins↗

PubMed1998

Effect of resistance exercise training on cortical and cancellous bone in mature male rats.

The effect of resistance training on tibial cancellous and cortical bone was evaluated in rats by using static histomorphometry and Northern analysis. Five-month-old male Sprague-Dawley rats were randomly assigned to exercise (Ex; n = 8) or control (Con; n = 4) groups. Animals were operantly conditioned to press two levers, facilitating full extension and flexion of the hindlimbs ("squats"), while wearing an unweighted vest. After an 8-wk familiarization period, Ex animals performed 3 sessions/wk for 17-19 sessions with progressively increased amounts of weight applied to the vest. Con rats completed the same exercise protocol without applied resistance. No difference in cross-sectional, medullary, or cortical bone area was observed between Ex and Con rats in the tibial diaphysis. In contrast, the cancellous bone area in the proximal tibial metaphysis was significantly larger in trained rats. Trabecular number, trabecular thickness, and the percentage of cancellous bone covered by osteoid were significantly greater in the Ex animals compared with Con animals. In addition, steady-state mRNA levels for osteocalcin for the Ex group were 456% those expressed in the Con group. The data demonstrate that resistance training increases cancellous bone area in sexually mature male rats and suggest that it does so, in part, by stimulating bone formation.

Animals↗

PubMed1997

Myonuclear loss in atrophied soleus muscle fibers.

BACKGROUND: A skeletal muscle fiber consists of many successive "territories," each controlled by the nucleus residing in that territory. Because nuclei appear to control a specific amount of territory (nuclear domain), nuclei must be added to accommodate an increase in fiber size. Because growth and hypertrophy require the addition of nuclei to fibers, it is of interest to determine whether atrophy causes a decrease in myonuclear number. This study compared the myonuclear population in the soleus muscles of rats that had undergone atrophy due to 10 days of spaceflight in the space shuttle, Endeavour, with muscles of ground-based control animals (10 rats each). METHODS: Myofibrillar ATPase activity was used to determine the major skeletal muscle fiber types in control rats and those having spent 10 days in space, and dystrophin antibodies were used to label the sarcolemma to identify underlying myonuclei. RESULTS: Type I and II fibers were atrophied after the flight, but type I fibers were atrophied twice as much as type II. Myonuclei were counted in identified and measured fibers, and the distribution normalized to number per millimeter of fiber circumference; this was significantly greater in type II than in type I fibers in both groups of rats. However, although the muscle fibers from flight animals were significantly atrophied, the normalized number of nuclei were identical between control and flight animals, indicating that nuclei decreased in numbers as the fibers atrophied. CONCLUSION: The nuclear domain is under strict control, and a decrease in the domain, as induced by atrophy, will cause nuclear degeneration and loss, which maintains a relatively constant size of the nuclear domain.

Adenosine Triphosphatases↗

PubMed1997

Direct interaction between amino- and carboxyl-terminal domains of cyclic nucleotide-gated channels.

We have examined domain interactions in the rod cyclic nucleotide-gated ion channel using both physiological and biochemical interaction assays. We have found an interaction between two regions of the channel distant in primary structure, the amino-terminal region and the carboxyl-terminal region containing the cyclic nucleotide-binding (CNB) domain. The interaction in functional channels was detected by the formation of a disulfide bond between cysteine residues at position 35 in the amino-terminal region and 481 in the carboxyl-terminal region. The disulfide bond resulted in channel potentiation, which was due, in part, to an increase in availability of C481 to modification when the channels were open. This state dependence is likely to underlie previously reported potentiation of cyclic nucleotide-gated channels by sulfhydryl-reactive compounds. Polypeptides derived from the amino-terminal and carboxyl-terminal regions were shown to interact, even under conditions which precluded disulfide bond formation. These data argue for a previously unknown, direct interaction between disparate regions of channel sequence.

Amino Acids↗

PubMed1997

Mechanism of tetracaine block of cyclic nucleotide-gated channels.

Local anesthetics are a diverse group of ion channel blockers that can be used to probe conformational changes in the pore. We examined the effects of the local anesthetic tetracaine on rod and olfactory cyclic nucleotide-gated channels expressed from subunit 1 in Xenopus oocytes. We found that 40 microM tetracaine effectively blocked the bovine rod channel but not the rat olfactory channel at saturating concentrations of cGMP. By testing chimeric channels containing regions of sequence from both rod and olfactory channels, we found that determinants of apparent affinity for tetracaine at saturating cGMP did not map to any one region of the channel sequence. Rather, the differences in apparent affinity could be explained by differences between the chimeras in the free energy of the opening allosteric transition. If a channel construct (such as the rod channel) spent appreciable time in the closed state at saturating cGMP, then it had a high apparent affinity for tetracaine. If, on the other hand, a channel construct (such as the olfactory channel) spent little time in the closed state at saturating cGMP, then it had a low apparent affinity for tetracaine. Furthermore, tetracaine became more effective at low concentrations of cGMP and at saturating concentrations of cAMP, conditions which permit the channels to spend more time in the closed configuration. These results were well fit by a model in which tetracaine binds more tightly to the closed channel than to the open channel. Dose-response curves for tetracaine in the presence of saturating cGMP are well fit with a Michaelis-Menten binding scheme indicating that a single tetracaine molecule is sufficient to produce block. In addition, tetracaine block is voltage dependent with an effective z delta of +0.56. These data are consistent with a pore-block hypothesis. The finding that tetracaine is a state-dependent pore blocker suggests that the inner mouth of the pore of cyclic nucleotide-gated channels undergoes a conformational change during channel opening.

Anesthetics, Local↗

PubMed1997

Physiological adaptations to a weight-loss dietary regimen and exercise programs in women.

Thirty-one women (mean age 35.4 +/- 8.5 yr) who were overweight were matched and randomly placed into either a control group (Con; n = 6), a diet-only group (D; n = 8), a diet+aerobic endurance exercise training group (DE; n = 9), or a diet+aerobic endurance exercise training+strength training group (DES; n = 8). After 12 wk, the three dietary groups demonstrated a significant (P </= 0.05) reduction in body mass, %body fat, and fat mass. No differences were observed in the magnitude of loss among groups, in fat-free mass, or in resting metabolic rate. The DE and DES groups increased maximal oxygen consumption, and the DES group demonstrated increases in maximal strength. Weight loss resulted in a similar reduction in total serum cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol among dietary groups. These data indicate that weight loss during moderate caloric restriction is not altered by inclusion of aerobic or aerobic+resistance exercise, but diet in conjunction with training can induce remarkable adaptations in aerobic capacity and muscular strength despite significant reductions in body mass.

Adaptation, Physiological↗

PubMed1996

Altered ligand specificity by protonation in the ligand binding domain of cyclic nucleotide-gated channels.

Cyclic nucleotide-gated (CNG) ion channels are the critical mediators between the second messengers of sensory transduction and the cell's membrane potential. The photoreceptor CNG channels are activated by the direct binding of cGMP but can also be activated to a much lesser extent by cAMP. In rod CNG channels expressed in Xenopus oocytes, we demonstrate two types of potentiation by protons. One type potentiated cGMP-bound and cAMP-bound channels to the same extent, while another potentiated only cAMP-bound channels. Both types of potentiation could be described by a mechanism in which protons bound primarily to the channel open configuration. The potentiation specific to cAMP-bound channels could be accounted for by protonation of aspartic acid 604 (D604). It is the unfavorable electrostatic interaction between the carboxylate of D604 and the purine ring of cAMP that accounts for the normally poor activation of the channels by cAMP. Protonation at this site removed the unfavorable interaction and allowed cAMP to act as nearly a full agonist. Protonation of a second amino acid, H468, contributed to the nucleotide-nonspecific potentiation and is likely to be an element of the channel gating assembly. Protons potentiate native rod channels less than channels formed from subunit 1. In heteromultimeric channels formed by coexpressing subunit 1 with subunit 2, we found a similar attenuation of potentiation. The absence of protonatable amino acids in subunit 2 at positions corresponding to H468 and D604 can explain the reduced effects of pH on native channels.

Animals↗