2009 Warm Springs Rd
Columbus GA 31904
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Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca(2+) signaling in dystrophic mdx mouse muscle. - American journal of physiology. Cell physiology
The majority of the skeletal muscle plasma membrane is internalized as part of the tubular (t-) system, forming a standing junction with the sarcoplasmic reticulum (SR) membrane throughout the muscle fiber. This arrangement facilitates not only a rapid and large release of Ca(2+) from the SR for contraction upon excitation of the fiber, but has also direct implications for other interdependent cellular regulators of Ca(2+). The t-system plasma membrane Ca-ATPase (PMCA) and store-operated Ca(2+) entry (SOCE) can also be activated upon release of SR Ca(2+). In muscle, the SR Ca(2+) sensor responsible for rapidly activated SOCE appears to be the stromal interacting molecule 1L (STIM1L) isoform of STIM1 protein, which directly interacts with the Orai1 Ca(2+) channel in the t-system. The common isoform of STIM1 is STIM1S, and it has been shown that STIM1 together with Orai1 in a complex with the partner protein of STIM (POST) reduces the activity of the PMCA. We have previously shown that Orai1 and STIM1 are upregulated in dystrophic mdx mouse muscle, and here we show that STIM1L and PMCA are also upregulated in mdx muscle. Moreover, we show that the ratios of STIM1L to STIM1S in wild-type (WT) and mdx muscle are not different. We also show a greater store-dependent Ca(2+) influx in mdx compared with WT muscle for similar levels of SR Ca(2+) release while normal activation and deactivation properties were maintained. Interestingly, the fiber-averaged ability of WT and mdx muscle to extrude Ca(2+) via PMCA was found to be the same despite differences in PMCA densities. This suggests that there is a close relationship among PMCA, STIM1L, STIM1S, Orai1, and also POST expression in mdx muscle to maintain the same Ca(2+) extrusion properties as in the WT muscle.
Longitudinal and transversal propagation of excitation along the tubular system of rat fast-twitch muscle fibres studied by high speed confocal microscopy. - The Journal of physiology
Mammalian skeletal muscle fibres possess a tubular (t-) system that consists of regularly spaced transverse elements which are also connected in the longitudinal direction. This tubular network provides a pathway for the propagation of action potentials (APs) both radially and longitudinally within the fibre, but little is known about the actual radial and longitudinal AP conduction velocities along the tubular network in mammalian skeletal muscle fibres. The aim of this study was to track AP propagation within the t-system network of fast-twitch rat muscle fibres with high spatio-temporal resolution when the t-system was isolated from the surface membrane. For this we used high speed confocal imaging of AP-induced Ca(2+) release in contraction-suppressed mechanically skinned fast-twitch fibres where the t-system can be electrically excited in the absence of the surface membrane. Supramaximal field pulses normally elicited a synchronous AP-induced release of Ca(2+) along one side of the fibre axis which propagated uniformly across the fibre. In some cases up to 80 or more adjacent transverse tubules failed to be excited by the field pulse, while adjacent areas responded with normal Ca(2+) release. In these cases a continuous front of Ca(2+) release with an angle to the scanning line was observed due to APs propagating longitudinally. From these observations the radial/transversal and longitudinal AP conduction velocities along the tubular network deeper in the fibre under our conditions (19 Â± 1Â°C) ranged between 8 and 11 Î¼m ms(-1) and 5 to 9 Î¼m ms(-1), respectively, using different methods of estimation. The longitudinal propagation of APs appeared to be markedly faster closer to the edge of the fibre, in agreement with the presence of dense longitudinal connections immediately below the surface of the fibre and more sparse connections at deeper planes within the fibre. During long trains of closely spaced field pulses the AP-elicited Ca(2+) releases became non-synchronous along the fibre axis. This is most likely caused by local tubular K(+) accumulation that produces local depolarization and local slowing of AP propagation. Longitudinally propagating APs may reduce such inhomogeneities by exciting areas of delayed AP onset. Clearly, the longitudinal tubular pathways within the fibre for excitation are used as a safety mechanism in situations where a local depolarization obstructs immediate excitation from the sarcolemma. Results obtained from this study also provide an explanation for the pattern of contractures observed in rippling muscle disease.
Qualitatively different cross-bridge attachments in fast and slow muscle fiber types. - Biochemical and biophysical research communications
Contractile properties differ between skeletal, cardiac and smooth muscles as well as between various skeletal muscle fiber types. This functional diversity is thought to be mainly related to different speeds of myosin head pulling cycles, with the molecular mechanism of force generation being essentially the same. In this study, force-generating attachments of myosin heads were investigated by applying small perturbations of myosin head pulling cycles in stepwise stretch experiments on skeletal muscle fibers of different type. Slow fibers (frog tonic and rat slow-twitch) exhibited only a 'slow-type' of myosin head attachment over the entire activation range, while fast fibers (frog and rat fast-twitch) displayed a 'slow-type' of myosin head attachment at low levels of activation, and an up to 30-times faster type at high levels of activation. These observations indicate that there are qualitative differences between the mechanisms of myosin head attachment in slow and fast vertebrate skeletal muscle fibers.
Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle. - The Journal of physiology
Periods of low frequency stimulation are known to increase the net Ca(2+) uptake in skeletal muscle but the mechanism responsible for this Ca(2+) entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca(2+) flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca(2+) in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca(2+)] ([Ca(2+)](t-sys)) and cytoplasmic [Ca(2+)] ([Ca(2+)](cyto)) were simultaneously resolved on a confocal microscope. When initial [Ca(2+)](t-sys) was > or = 0.2 mM a Ca(2+) flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca(2+) flux and associated t-system Ca(2+) permeability decayed exponentially and displayed inactivation characteristics such that further Ca(2+) entry across the t-system could not be observed after 2-3 action potentials at 10 Hz stimulation rate. When [Ca(2+)](t-sys) was closer to 0.1 mM, a transient rise in [Ca(2+)](t-sys) was observed almost concurrently with the increase in [Ca(2+)](cyto) following the action potential. The change in direction of Ca(2+) flux was consistent with changes in the direction of the driving force for Ca(2+). This is the first demonstration of a rapid t-system Ca(2+) flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca(2+) channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca(2+) flux provides an explanation for the previously described Ca(2+) entry and accumulation observed with prolonged, intermittent muscle activity.
Effect of temperature-induced reactive oxygen species production on excitation-contraction coupling in mammalian skeletal muscle. - Clinical and experimental pharmacology & physiology
1. Here we review evidence obtained recently by us indicating that the poor longevity of isolated mammalian skeletal muscle preparations at temperatures in the normal physiological range is related to the increased production of reactive oxygen species (ROS) in the resting muscle. 2. Temperature-induced ROS production increases markedly above 32 degrees C in isolated, resting skeletal muscle and is associated with the gradual and irreversible functional deterioration of the muscle. 3. The majority of the temperature-induced muscle ROS originates in the mitochondria and acts on various sites involved in excitation-contraction coupling.
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2009 Warm Springs Rd Columbus, GA 31904
2300 Manchester Expy Suite 101A
2300 Manchester Expy Butler Pavilion, Ste B001