The foundation of excitation-contraction coupling in skeletal muscle: communication between the transverse tubules and sarcoplasmic reticulum.

The expression excitation-contraction (EC) coupling in skeletal muscle was coined in 1952 (Sandow A. 25: 176-201, 1952). The term evolved narrowly to include only the processes at the triad that intervene between depolarization of the transverse tubular (T-tubular) membrane and Ca release from the sarcoplasmic reticulum (SR).

The dawn of muscle energetics: contraction before and after discovery of ATP.

By the beginning of the twentieth century, vitalism was generally rejected and it was accepted that biological organisms obeyed the laws of physics and chemistry. Muscle contraction was thought to be fueled by a chemical reaction. The dawn of muscle energetics began in the early twentieth century when Otto Meyerhof and A.

Discovery of the regulatory role of calcium ion in muscle contraction and relaxation: Setsuro Ebashi and the international emergence of Japanese muscle research.

In the early 1950s Setsuro Ebashi was a graduate student at Tokyo University studying the biochemical models of muscle contraction. The muscle components in these models contracted in the presence of ATP, but what caught his attention was that the components did not relax when ATP was exhausted. Ebashi decided in 1952 to attempt to elucidate the mechanism of muscle relaxation using these models.

Investigation of the molecular motor of muscle: from generating life in a test tube to myosin structure over beers.

This article traces 60 years of investigation of the molecular motor of skeletal muscle from the 1940s through the 1990s. It started with the discovery that myosin interaction with actin in the presence of ATP caused shortening of threads of actin and myosin. In 1957, structures protruding from myosin filaments were seen for the first time and called "cross bridges.

A perfect confluence of physiology and morphology: discovery of the transverse tubular system and inward spread of activation in skeletal muscle.

By early 1954, there existed a plausible model of muscle contraction called the sliding filament model. In addition, the nature of muscle excitation was understood. Surprisingly, the link between the membrane excitation and contraction was entirely unknown.

Calcium and muscle contraction: the triumph and tragedy of Lewis Victor Heilbrunn.

Lewis Victor Heilbrunn has been called the pioneer of Ca as an intracellular regulator (Campbell AK. 7: 287-296, 1986; Campbell AK. , 2015).

What makes skeletal muscle striated? Discoveries in the endosarcomeric and exosarcomeric cytoskeleton.

One of the most iconic images in biology is the cross-striated appearance of a skeletal muscle fiber. The repeating band pattern shows that all of the sarcomeres are the same length. All of the A bands are the same length and are located in the middle of the sarcomeres.

Generation of life in a test tube: Albert Szent-Gyorgyi, Bruno Straub, and the discovery of actin.

This is a story about a great scientist, luck, great discovery that changed the future direction of muscle research, war, a clandestine war mission, postwar politics, and an attempt to rewrite scientific history. Albert Szent-Gyorgyi, at 44 yr of age, won the Nobel Prize in 1937 for his work on vitamin C and the establishment of the groundwork of the citric acid cycle. He now wanted to investigate one of the fundamental aspects of life and settled on the study of muscle contraction.

Nobel Laureate A. V. Hill and the refugee scholars, 1933-1945.

A. V. Hill shared the 1922 Nobel Prize in Physiology or Medicine for his investigation of the energetics of muscular contraction.

The XIIIth International Physiological Congress in Boston in 1929: American physiology comes of age.

In the 19th century, the concept of experimental physiology originated in France with Claude Bernard, evolved in Germany stimulated by the teaching of Carl Ludwig, and later spread to Britain and then to the United States. The goal was to develop a physicochemical understanding of physiological phenomena. The first International Physiological Congress occurred in 1889 in Switzerland with an emphasis on experimental demonstrations.

Effect of Ca2+ binding properties of troponin C on rate of skeletal muscle force redevelopment.

To investigate effects of altering troponin (Tn)C Ca(2+) binding properties on rate of skeletal muscle contraction, we generated three mutant TnCs with increased or decreased Ca(2+) sensitivities. Ca(2+) binding properties of the regulatory domain of TnC within the Tn complex were characterized by following the fluorescence of an IAANS probe attached onto the endogenous Cys(99) residue of TnC. Compared with IAANS-labeled wild-type Tn complex, V43QTnC, T70DTnC, and I60QTnC exhibited ∼1.

Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities.

We investigated whether changing thin filament Ca(2+) sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (P(i)). We increased or decreased Ca(2+) sensitivity of force production by incorporating into rat skinned cardiac trabeculae the troponin C (TnC) mutants V44QTnC(F27W) and F20QTnC(F27W). The rate of isometric contraction was assessed as the rate of force redevelopment (k(tr)) after a rapid release and restretch to the original length of the muscle.

Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C.

The influences of [Ca(2+)] and Ca(2+) dissociation rate from troponin C (TnC) on the kinetics of contraction (k(Ca)) activated by photolysis of a caged Ca(2+) compound in skinned fast-twitch psoas and slow-twitch soleus fibers from rabbits were investigated at 15 degrees C. Increasing the amount of Ca(2+) released increased the amount of force in psoas and soleus fibers and increased k(Ca) in a curvilinear manner in psoas fibers approximately 5-fold but did not alter k(Ca) in soleus fibers. Reconstituting psoas fibers with mutants of TnC that in solution exhibited increased Ca(2+) affinity and approximately 2- to 5-fold decreased Ca(2+) dissociation rate (M82Q TnC) or decreased Ca(2+) affinity and approximately 2-fold increased Ca(2+) dissociation rate (NHdel TnC) did not affect maximal k(Ca).

Energetics, mechanics and molecular engineering of calcium cycling in skeletal muscle.

During muscle contraction and relaxation, Ca2+ moves through a cycle. About 20 to 40% of the ATP utilized in a twitch or a tetanus is utilized by the SR Ca2+ pump to sequester Ca2+. Parvalbumin is a soluble Ca2+ binding protein that functions in parallel with the SR Ca2+ pump to promote relaxation in rapidly contracting and relaxing skeletal muscles, especially at low temperatures.

Myofibrillar determinants of rate of relaxation in skinned skeletal muscle fibers.

The influence of Ca2+ dissociation rate from TnC and decreased cross-bridge detachment rate on the time course of relaxation induced by flash photolysis of diazo-2 in rabbit skinned psoas fibers was investigated at 15 degrees C. A TnC mutant (M82Q TnC) that exhibited increased Ca2+ sensitivity caused by a decreased Ca2+ dissociation rate in solution also increased the Ca2+ sensitivity of force and decreased the rate of relaxation in fibers approximately 2-fold. In contrast, a TnC mutant (NHdel TnC) with decreased Ca2+ sensitivity caused by an increased Ca2+ dissociation rate in solution decreased Ca2+ sensitivity of force but did not accelerate relaxation.

Mutations of hydrophobic residues in the N-terminal domain of troponin C affect calcium binding and exchange with the troponin C-troponin I96-148 complex and muscle force production.

Interactions between troponin C and troponin I play a critical role in the regulation of skeletal muscle contraction and relaxation. We individually substituted 27 hydrophobic Phe, Ile, Leu, Val, and Met residues in the regulatory domain of the fluorescent troponin C(F29W) with polar Gln to examine the effects of these mutations on: (a) the calcium binding and dynamics of troponin C(F29W) complexed with the regulatory fragment of troponin I (troponin I(96-148)) and (b) the calcium sensitivity of force production. Troponin I(96-148) was an accurate mimic of intact troponin I for measuring the calcium dynamics of the troponin C(F29W)-troponin I complexes.

Determinants of relaxation rate in rabbit skinned skeletal muscle fibres.

The influence of Ca(2+)-activated force, the rate of dissociation of Ca(2+) from troponin C (TnC) and decreased crossbridge detachment rate on the time course of relaxation induced by flash photolysis of diazo-2 in rabbit skinned psoas fibres was investigated at 15 degrees C. The rate of relaxation increased as the diazo-2 chelating capacity (i.e.

Engineering competitive magnesium binding into the first EF-hand of skeletal troponin C.

The goal of this study was to examine the mechanism of magnesium binding to the regulatory domain of skeletal troponin C (TnC). The fluorescence of Trp(29), immediately preceding the first calcium-binding loop in TnC(F29W), was unchanged by addition of magnesium, but increased upon calcium binding with an affinity of 3.3 microm.

Effect of hydrophobic residue substitutions with glutamine on Ca(2+) binding and exchange with the N-domain of troponin C.

Troponin C (TnC) is an EF-hand Ca(2+) binding protein that regulates skeletal muscle contraction. The mechanisms that control the Ca(2+) binding properties of TnC and other EF-hand proteins are not completely understood. We individually substituted 27 Phe, Ile, Leu, Val, and Met residues with polar Gln to examine the role of hydrophobic residues in Ca(2+) binding and exchange with the N-domain of a fluorescent TnC(F29W).