LAUSR

Bernhard Brenner, M.D., professor and chairman of physiology at the Medical School of Hannover, Germany, died on June 26th, 2017 after a courageous fight against cancer. He was 66. Bernhard was a scientist with a razor sharp intellect and an unyielding zeal to elucidate the mechanism of muscle contraction. He will be fondly remembered as an inspiring colleague and mentor to many. Bernhard was born in Stuttgart, Germany. He studied Medicine at the University of Tübingen from 1969 to 1975 and received his doctoral degree in 1979. For his thesis he studied strain-induced calcium release from striated muscle sarcoplasmic reticulum with Professor Rudhard Jacob. He demonstrated independence and a talent for innovative experimental approaches early on in his career. Bernhard designed and built his own devices for measuring fast mechanical kinetics of single muscle fibers. He perfected the preparation of permeabilized single mammalian (rabbit) skeletal muscle fibers with control over the bathing medium. He discovered that repeated cycles of stretches and quick releases of a muscle fiber under fully activating conditions could keep the striation pattern stable for hours without deterioration. Later such cycles were dubbed by some colleagues as the “Brenner Cycles” and are still a standard method in muscle labs. From 1980 to 1985 Bernhard was a visiting research associate in the laboratory of Richard Podolsky at the National Institutes of Health (NIH), USA. While at NIH, a rather close-knit and long lasting collaborative group was formed, which included Richard Podolsky, Evan Eisenberg, Joseph Chalovich, Lois Greene, Mark Schoenberg, Leepo Yu and Bernhard. The group took advantage of the fact that, for the first time, biochemical, mechanical and structural results could be obtained under the same experimental conditions. Biochemical results were previously obtained from rabbit muscle whereas mechanical and structural (X-ray diffraction) results were measured in frog muscle. At the time the Eisenberg lab proposed the existence of weak binding states within the actomyosin ATP hydrolysis cycle. Bernhard’s high-speed mechanical and X-ray diffraction measurements provided the first evidence of these weak binding states in muscle fibers. The results indicated that tropomyosin-troponin does not block cross-bridge binding to actin in relaxed muscle, contrary to the widely accepted “steric blocking” model of muscle regulation. Further experiments showed that the specific attachment of cross-bridges to actin in the weak binding states is essential in the pathway to contraction. He showed that, rather than controlling the binding of myosin to actin, tropomyosin-troponin regulates contraction by altering the rate of cross-bridge cycling kinetics. Calcium shifts the equilibrium between the inactive and active forms of actin-tropomyosin-troponin to the active form that has rapid cycling kinetics. The conclusion that calcium regulates cross-bridge kinetics in muscle fibers came from the experimental protocol that Bernhard used. Muscle fibers in a medium with a defined calcium concentration were subjected to a short period of unloaded shortening followed by re-stretch to * Theresia Kraft [email protected]