Chronic resistance training: is it time to rethink the time course of neural contributions to strength gain?

Resistance training enhances muscular force due to a combination of neural plasticity and muscle hypertrophy. It has been well documented that the increase in strength over the first few weeks of resistance training (i.e. acute) has a strong underlying neural component and further enhancement in strength with long-term (i.e. chronic) resistance training is due to muscle hypertrophy. For obvious reasons, collecting long-term data on how chronic-resistance training affects the nervous system not feasible. As a result, the effect of chronic-resistance training on neural plasticity is less understood and has not received systematic exploration. Thus, the aim of this review is to provide rationale for investigating neural plasticity beyond acute-resistance training. We use cross-sectional work to highlight neural plasticity that occurs with chronic-resistance training at sites from the brain to spinal cord. Specifically, intra-cortical circuitry and the spinal motoneuron seem to be key sites for this plasticity. We then urge the need to further investigate the differential effects of acute versus chronic-resistance training on neural plasticity, and the role of this plasticity in increased strength. Such investigations may help in providing a clearer definition of the continuum of acute and chronic-resistance training, how the nervous system is altered during this continuum and the causative role of neural plasticity in changes in strength over the continuum of resistance training.

Short-interval intracortical inhibition to the biceps brachii is present during arm cycling but is not different than a position- and intensity-matched tonic contraction.

We have previously shown that supraspinal excitability is higher during arm cycling than a position- and intensity-matched tonic contraction. The present study sought to determine if short-interval intracortical inhibition (SICI) was present during arm cycling and if so, if the amount of SICI was different from an intensity-matched tonic contraction. SICI was assessed using conditioning stimuli (CS) of 70 and 90% of active motor threshold (AMT) and a test stimulus (TS) of 120% AMT at an interstimulus interval (ISI) of 2.5 ms. SICI was elicited in all participants; on average (i.e., cycling and tonic contraction grouped) test MEP amplitudes were reduced by 64.2% (p < 0.001) and 62.8% (p = 0.001) following conditioning stimuli of 70% and 90% AMT, respectively. There was no significant difference in extent of SICI between tasks (p = 0.360). These data represent the novel finding that SICI is present during arm cycling, a motor output partially mediated by spinal interneuronal networks. The amount of SICI, however, was not different from that during a position- and intensity-matched tonic contraction, suggesting that SICI is not likely a cortical mechanism contributing to higher supraspinal excitability during arm cycling compared to tonic contraction.

Intensity matters: effects of cadence and power output on corticospinal excitability during arm cycling are phase and muscle dependent.

The present study investigated the effects of cadence and power output on corticospinal excitability to the biceps (BB) and triceps brachii (TB) during arm cycling. Supraspinal and spinal excitability were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract, respectively. Motor-evoked potentials (MEPs) elicited by TMS and cervicomedullary motor-evoked potentials (CMEPs) elicited by TMES were recorded at two positions during arm cycling corresponding to mid-elbow flexion and mid-elbow extension (i.e., 6 and 12 o'clock made relative to a clock face, respectively). Arm cycling was performed at combinations of two cadences (60 and 90 rpm) at three relative power outputs (20, 40, and 60% peak power output). At the 6 o'clock position, BB MEPs increased ~11.5% as cadence increased and up to ~57.2% as power output increased ( P < 0.05). In the TB, MEPs increased ~15.2% with cadence ( P = 0.013) but were not affected by power output, while CMEPs increased with cadence (~16.3%) and power output (up to ~19.1%, P < 0.05). At the 12 o'clock position, BB MEPs increased ~26.8% as cadence increased and up to ~96.1% as power output increased ( P < 0.05), while CMEPs decreased ~29.7% with cadence ( P = 0.013) and did not change with power output ( P = 0.851). In contrast, TB MEPs were not different with cadence or power output, while CMEPs increased ~12.8% with cadence and up to ~23.1% with power output ( P < 0.05). These data suggest that the "type" of intensity differentially modulates supraspinal and spinal excitability in a manner that is phase- and muscle dependent. NEW & NOTEWORTHY There is currently little information available on how changes in locomotor intensity influence excitability within the corticospinal pathway. This study investigated the effects of arm cycling intensity (i.e., alterations in cadence and power output) on corticospinal excitability projecting to the biceps and triceps brachii during arm cycling. We demonstrate that corticospinal excitability is modulated differentially by cadence and power output and that these modulations are dependent on the phase and the muscle examined.

Plasticity of rat motoneuron rhythmic firing properties with varying levels of afferent and descending inputs.

Hindlimb motoneuron excitability was compared among exercise-trained (E), sedentary (S), and spinal cord transected (T) Sprague-Dawley rats by examining the slope of the frequency-current (F/I) relationship with standard intracellular recording techniques in rats anesthetized with ketamine-xylazine. The T group included spinal transected and spinal isolated rats; the E animals were either spontaneously active (exercise wheel) or treadmill trained; and rats in the S group were housed in pairs. An analysis of motoneuron initial [1st interspike interval (ISI)], early (mean of 1st three ISIs), and steady-state (mean of last 3 ISIs) discharge rate slopes resulting from increasing and decreasing 500-ms injected square-wave depolarizing current pulses was used to describe rhythmic motoneuron properties. The steepest slope occurred in the S group (55.3 ± 22.2 Hz/nA), followed by the T group (35.5 ± 15.3 Hz/nA), while the flattest slope was found in the E group (25.4 ± 10.9 Hz/nA). The steepest steady-state slope occurred in the S group but was found to be similar between the T and E groups. Furthermore, a spike-frequency adaptation (SFA) index revealed a slower adaptation in motoneurons of the E animals only (∼40% lower). Finally, evidence for a secondary range of firing existed more frequently in the T group (41%) compared with the S (12%) and E (31%) groups. The lower F/I slope and lower SFA index of motoneurons for E rats may be a result of an increase in Na(+) conductance at the initial segment. The results show that motoneuronal rhythmic firing behavior is plastic, depending on the volume of daily activation and on intact descending pathways.

Investigation of Localized Skin Temperature Distribution Across the Transtibial Residual Limb.

BACKGROUND: Interventions to resolve thermal discomfort as a common complaint in amputees are usually chosen based on the residual limb skin temperature while wearing prosthesis; whereas, less attention has been paid to residual limb skin temperature while outside of the prosthesis. The objective of this study was to explore the localized and regional skin temperature over the transtibial residual limb (TRL) while outside of the prosthesis. METHODOLOGY: Eight unilateral transtibial adults with traumatic amputation were enrolled in this cross-sectional study. Participants sat to remove their prostheses and rested for 30 minutes. Twelve sites were marked circumferentially in four columns (anterolateral, anteromedial, posteromedial, and posterolateral) and longitudinally in three rows (proximal, middle, and distal) over the residual limb and used for attachment of analog thermistors. Skin temperature was recorded and compared for 11 minutes. Furthermore, the relationship of skin temperature with participants' demographic and clinical characteristics was explored. FINDINGS: The whole temperature of the TRL was 27.73 (SD=0.83)°C. There was a significant difference in skin temperature between anterior and posterior columns. Likewise, the distal row was significantly different from the proximal and middle rows. The mean temperature at the middle and distal zones of the anteromedial column had the highest and lowest skin temperatures (29.8 and 26.3°C, p<0.05), respectively. The mean temperature of the whole TRL had no significant relationships (p>0.05) with participants' demographic and clinical characteristics. CONCLUSIONS: An unequal distribution of temperature over the TRL was found with significantly higher and lower temperatures at its anterior column and distal row, respectively. This temperature pattern should be considered for thermoregulation strategies. Further investigation of the residual limb temperature with and without prosthesis, while considering muscles thickness and blood perfusion rate is warranted.

Neuromuscular fatigue of the elbow flexors during repeated maximal arm cycling sprints: the effects of forearm position.

Repeated sprint exercise (RSE) is often used to induce neuromuscular fatigue (NMF). It is currently not known whether NMF is influenced by different forearm positions during arm cycling RSE. The purpose of this study was to investigate the effects of a pronated versus supinated forearm position on elbow flexor NMF during arm cycling RSE. Participants (n = 12) completed ten 10-s maximal arm cycling sprints interspersed by 60 s of rest on 2 separate days using either a pronated or supinated forearm position. All sprints were performed on an arm cycle ergometer in a reverse direction. Prior to and following RSE, NMF measurements (i.e., maximal voluntary contraction (MVC), potentiated twitch (PT), electromyography median frequencies) were recorded. Sprint performance measures, ratings of perceived exertion (RPE) and pain were also recorded. Irrespective of forearm position, sprint performance decreased as sprint number increased. These decreases were accompanied by significant increases in RPE (p < 0.001, ηp2 = 0.869) and pain (p < 0.001, ηp2 = 0.745). Participants produced greater power output during pronated compared with supinated sprinting (p < 0.001, ηp2 = 0.728). At post-sprinting, the percentage decrease in elbow flexor MVC and PT force from pre-sprinting was significantly greater following supinated than pronated sprinting (p < 0.001), suggesting greater peripheral fatigue occurred in this position. The data suggest that supinated arm cycling RSE results in inferior performance and greater NMF compared with pronated arm cycling RSE. Novelty: NMF of the elbow flexors is influenced by forearm position during arm cycling RSE. Supinated arm cycling sprints resulted in worse repeated sprint performance and also greater NMF than pronated RSE.

Measurement of cytoplasmic calcium concentration in cell suspensions: correction for extracellular Fura-2 through use of Mn2+ and probenecid.

1321N1 astrocytoma cells loaded with Fura-2 were found to continuously transport Fura-2 to the extracellular medium. To correct for extracellular Fura-2 fluorescence a protocol was developed in which Mn2+ was added to duplicate cuvettes of cells to quench extracellular Fura-2 at the beginning and end of the experimental time course. Since the export of Fura-2 was linear with time, two separate quench determinations allowed the amount of fluorescence from extracellular Fura-2 fluorescence to be estimated at every point in the time course and subtracted from the data. The uncorrected and Mn2+-corrected basal cytoplasmic calcium concentrations averaged 153 nM and 72 nM, respectively. The peak intracellular calcium concentrations following muscarinic stimulation with 300 microM carbachol averaged 1159 nM (uncorrected) and 889 nM (Mn2+-corrected). Probenecid (2.5 mM) was found to block the export of Fura-2 from these cells and did not change the basal calcium concentration or the muscarinic calcium response.

Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain.

Gastric inhibitory polypeptide (GIP), or glucose-dependent insulinotropic peptide, is released from endocrine cells in the small intestine after meals. It is involved in several facets of the anabolic response and is thought to be particularly important in stimulating insulin secretion. We have cloned, functionally expressed, and mapped the distribution of the receptor for GIP. It is a member of the secretin-vasoactive intestinal polypeptide family of G-protein-coupled receptors. When expressed in tissue culture cells, it stimulates cAMP production (EC50 0.3 nM) and also increases intracellular calcium accumulation. GIP receptor mRNA is present in the pancreas as well as the gut, adipose tissue, heart, pituitary, and inner layers of the adrenal cortex, whereas it is not found in kidney, spleen, or liver. It is also expressed in several brain regions, including the cerebral cortex, hippocampus, and olfactory bulb. These results suggest that GIP may have previously undescribed actions. GIP receptor localization in the adrenal cortex suggests that it may have effects on glucocorticoid metabolism. Neither GIP nor its effects have been described in the central nervous system, and mRNA for the known peptide ligand for the receptor cannot be detected in the brain by in situ hybridization or polymerase chain reaction. This suggests that a novel peptide may be present in the brain.

Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes.

In addition to their well-known functions in cellular energy transduction, mitochondria play an important role in modulating the amplitude and time course of intracellular Ca(2+) signals. In many cells, mitochondria act as Ca(2+) buffers by taking up and releasing Ca(2+), but this simple buffering action by itself often cannot explain the organelle's effects on Ca(2+) signaling dynamics. Here we describe the functional interaction of mitochondria with store-operated Ca(2+) channels in T lymphocytes as a mechanism of mitochondrial Ca(2+) signaling. In Jurkat T cells with functional mitochondria, prolonged depletion of Ca(2+) stores causes sustained activation of the store-operated Ca(2+) current, I(CRAC) (CRAC, Ca(2+) release-activated Ca(2+)). Inhibition of mitochondrial Ca(2+) uptake by compounds that dissipate the intramitochondrial potential unmasks Ca(2+)-dependent inactivation of I(CRAC). Thus, functional mitochondria are required to maintain CRAC-channel activity, most likely by preventing local Ca(2+) accumulation near sites that govern channel inactivation. In cells stimulated through the T-cell antigen receptor, acute blockade of mitochondrial Ca(2+) uptake inhibits the nuclear translocation of the transcription factor NFAT in parallel with CRAC channel activity and [Ca(2+)](i) elevation, indicating a functional link between mitochondrial regulation of I(CRAC) and T-cell activation. These results demonstrate a role for mitochondria in controlling Ca(2+) channel activity and signal transmission from the plasma membrane to the nucleus.

Factors affecting force loss with prolonged stretching.

The purpose of this study was to investigate the factors underlying the force loss occurring after prolonged, static, passive stretching. Subjects were tested before and 5-10 min following 20 min of static, passive stretching of the quadriceps (N=12) or a similar period of no stretch (control, N=6). Measurements included isometric maximal voluntary contraction (MVC) force, surface integrated electromyographic (iEMG) activity of the quadriceps and hamstrings, evoked contractile properties (twitch and tetanic force), and quadriceps inactivation as measured by the interpolated twitch technique (ITT). Following stretching, there was a significant 12% decrement in MVC with no significant changes in the control group. Muscle inactivation as measured by the ITT and iEMG increased by 2.8% and 20.2%, respectively. While twitch forces significantly decreased 11.7%, there was no change in tetanic force post-stretch. Although possible increases in muscle compliance affected twitch force, a lack of tetanic force change would suggest that post-stretch force decrements are more affected by muscle inactivation than changes in muscle elasticity.

Agonist regulation of alpha 1B-adrenergic receptor subcellular distribution and function.

We have monitored agonist-induced alpha 1B-adrenergic receptor (alpha 1BAR) redistribution by immunocytochemical procedures in concert with functional measurements of agonist-elicited [3H]inositol phosphate (InsP) production in human embryonal kidney 293 cells stably expressing alpha 1BAR cDNA (HEK293/alpha 1B). Anti-peptide antibodies directed against the carboxyl-terminal decapeptide of the alpha 1BAR were prepared and shown to react specifically with alpha 1BAR on immunoblots and in situ in HEK293/alpha 1B transfectants. Treatment of HEK293/alpha 1B cells with norepinephrine (10 microM) results in a rapid (5-15 min) and striking internalization of cell surface receptor as visualized by confocal immunofluorescence microscopy. Receptor redistribution is sustained in the presence of agonist, rapidly reversed upon agonist removal, and prevented by the alpha 1 antagonist prazosin. Receptor internalizes to endosomes, as shown by colocalization with transferrin receptor, an endosomal marker. Activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (50 nM) causes receptor endocytosis similar to agonist; agonist-induced internalization is blocked by the PKC inhibitor staurosporine (0.5 microM). In parallel experiments, agonist-induced [3H]InsP production is abolished by phorbol 12-myristate 13-acetate but potentiated by staurosporine. Inhibition of receptor internalization with hypertonic sucrose attenuates agonist-induced [3H]InsP formation; this effect is reversed by concomitant inhibition of PKC with staurosporine. These results suggest that PKC-dependent phosphorylation occurring as a consequence of alpha 1AR stimulation induces receptor desensitization and internalization. Internalized receptor is reactivated and continuously recycled to the cell surface during agonist exposure.

Extrapituitary expression of the rat V1b vasopressin receptor gene.

[Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned V1a and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the V1a and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.