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G F Tibbits

Publications and source records attributed to G F Tibbits.

26 records · Page 2Linked to original sources
PubMed1989

Ca2+ transport across the plasma membrane of striated muscle.

In both types of striated muscle (skeletal and cardiac), calcium flux across the plasma membrane (sarcolemma) is regulated by at least three distinct membrane proteins; a voltage-dependent Ca2+ channel, Ca2+ pump (Ca2+ ATPase), and the Na+/Ca2+ antiporter. Each of these proteins is subject to regulation by intracellular second messengers. The magnitude and the role of this transsarcolemmal calcium flux are quite different between cardiac and skeletal muscle. In cardiac muscle, the influx is large, precedes, and is obligatory for contraction. There is general agreement that this influx is the trigger for Ca2+ release from the sarcoplasmic reticulum (SR) in the heart according to the Ca2+-induced Ca2+ release hypothesis. Variations in the transsarcolemmal Ca2+ influx have a profound effect on the strength of cardiac contraction, and it appears that this is the primary physiological strategy for regulation of contractility. In skeletal muscle, on the other hand, the T-tubules represent the richest source of dihydropyridine (DHP)-sensitive calcium channels known to exist, yet the influx of Ca2+ is proportionally much smaller and a significant portion enters the fiber following the twitch. While the majority of the Ca2+ influx is twitch dependent, it is quite clear that contraction in skeletal muscle is not predicated on this influx. It has been proposed that these DHP channels act as voltage sensors in order to initiate release of SR Ca2+; however, the link between the sensors and the opening of the SR Ca2+ (ryanodine-sensitive) channel is unknown. Transsarcolemmal Ca2+ transport appears to be subject to intense regulation to modify the acute response and demonstrates some plasticity in the adaptation to chronic perturbations.

Biological Transport↗
PubMed1985

Na+-dependent alkaline earth metal uptake in cardiac sarcolemmal vesicles.

The ability of alkaline earth metals (M2+) to substitute for Ca2+ in Na+-Ca2+ exchange was examined in sarcolemmal vesicles isolated from the canine heart. 85Sr2+ and 133Ba2+, in addition to 45Ca2+, were used to determine the characteristics of Na+-M2+ exchange. The Na+i-dependent M2+ uptake was measured as a function of time, with t ranging from 0.5 to 360 s, [Na+]i = 140 mM and [M2+]o = 40 microM. This function was linear for Ca2+ and Sr2+ uptake for approx. 6 s and for Ba2+ for about 60 s. Plateau levels were achieved within 120 s for Ca2+ and Sr2+ but Ba2+ took considerably longer. The Km values for Na+-M2+ exchange, derived from Eadie-Hofstee plots, were 30, 58, and 73 microM for Ca2+, Sr2+ and Ba2+, respectively. The Na+i-dependent uptake of all three ions was stimulated in the presence of 0.36 microM valinomycin. Na+-Ca2+ exchange was also measured in the presence of either 20 microM Sr2+ or 100 microM Ba2+. Both of these ions behaved (at these concentrations) as competitive inhibitors of Na+-Ca2+ exchange with the KI being 32 microM for Sr2+ and 92 microM for Ba2+. Passive efflux was determined by first allowing Na+-M2+ exchange to continue to plateau values and then diluting the loaded vesicles in the presence of EGTA. The rate constants for the passive efflux were 8.4, 6.3 and 4.4 min-1 for Ca2+, Sr2+ and Ba2+, respectively.

Animals↗
PubMed1985

Regulation of myocardial contractility in exhaustive exercise.

The impact of exhaustive exercise on myocardial function is poorly understood. Experimental parameters of contractility that are completely devoid of other influences do not exist. Furthermore, the problem is compounded by the fact that exhaustive work comprises myriad exercise paradigms and fatigue may be the result of numerous possible mechanisms. Despite these confounding variables, there is evidence that stroke volume may be impaired by prolonged work in humans. These studies implicated reduced venous return and not contractility as the reason. Experiments with the rat model have indicated that treadmill running at about 60% of VO2max results in reduced isometric twitch tension in isolated trabecular tissue. The data are consistent with the notion that contractility is substantially reduced. The mechanism for this inhibition is unknown. In separate studies using a similar model, it has been shown that Ca2+ uptake by the sarcoplasm reticulum of the myocardium in vitro is reduced by fatigue. It is conceivable that in exhaustive exercise, there may be only a slight effect on contractility in vivo but that substantial adjustments in intracellular homeostasis are required in order to achieve this. Future considerations should include a rigorous analysis of contractility and the factors that regulate it, as well as the choice of animal and exhaustion models.

Acidosis↗
PubMed1981

Cardiac sarcolemma: compositional adaptation to exercise.

Marked changes were observed in the lipid composition of highly purified plasma membranes isolated from the hearts of rats subjected to daily treadmill running. Compared to sedentary controls, sarcolemmal content of total phospholipid and phosphatidylserine in the trained group was increased 23 and 50 percent, respectively. This observation suggests a mechanism by which cardiac contractility may be enhanced by exercise.

Adaptation, Physiological↗
PubMed1981

Influence of exercise on excitation-contraction coupling in rat myocardium.

The present studies were conducted to investigate further the mechanisms by which the myocardium adapts to exercise training. Sixty female rats were randomly divided into sedentary control (group C) and trained (group T) groups. Group T was progressively trained for 12 wk. After the rats were killed, left ventricular papillary muscles were mounted in a tissue bath for mechanical studies. Muscles from group T generated greater peak isometric twitch tension per unit cross-sectional area than muscles from group C with [Ca2+]o ranging from 0.25 to 3.5 mM. Analyses of these data indicated that the Km for Ca2+ was not different but that the predicted number of sarcolemmal Ca2+ binding sites was 63% higher in group T. The ATPase activity of the purified cardiac myofibrils was not different between the two groups in the pCa range of 8.53-4.42. Action potentials were recorded with microelectrodes impaled into left ventricular muscle fibers of the subendocardium. Although there was no difference in the resting membrane potential, overshoot, or 90% duration, there was a significant prolongation of the action potential at 0 mV (20.2 +/- 1.0 vs 30.0 +/- 1.3 ms) in group T. These data further support the hypothesis that treadmill exercise enhances cardiac performance by increasing Ca2+ availability to the contractile element. This adaptation is mediated, at least in part, by a sarcolemmal adaptation induced by the exercise paradigm.

Action Potentials↗
PubMedDate not supplied

Evolutionary and physiological variation in cardiac troponin C in relation to thermal strategies of fish.

Striated muscle contraction is initiated when troponin C (TnC) binds Ca(2+), which activates actinomyosin ATPase. We investigated (i) the variation between cardiac TnC (cTnC) primary structure within teleost fish and (ii) the pattern of TnC expression in response to temperature acclimation. There were few differences between rainbow trout (Oncorhynchus mykiss), yellowfin tuna (Thunnus albacares), yellow perch (Perca flavescens), goldfish (Carassius auratus), white sucker (Catostomus commersoni), and icefish (Chaenocephalus aceratus) in cTnC amino acid sequence. No variation existed in the regulatory Ca(2+)-binding site (site 2). The site 3 and 4 substitutions were limited to residues not directly involved in Ca(2+) coordination. Fish cTnC primary structure was highly conserved between species (93%-98%) and collectively divergent from the highly conserved sequence seen in birds and mammals. Northern blots and polymerase chain reaction showed that thermal acclimation of trout (3 degrees, 18 degrees C) did not alter the TnC isoform pattern. While cardiac and white muscle had the expected isoforms-cTnC and fast troponin C (fTnC), respectively-red muscle unexpectedly expressed primarily ftnC. Cold acclimation did not alter myofibrillar ATPase Ca(2+) sensitivity, but maximal velocity increased by 60%. We found no evidence that TnC variants, arising between species or in response to thermal acclimation, play a major role in mitigating the effects of temperature on contractility of the adult fish heart.

Adaptation, Physiological↗