W. Chandler MD

Professor Emeritus of Cellular and Molecular Physiology

Research Interests

Cell Physiology, Electrophysiology, Human Physiology, Muscle Structure or Function, Calcium, Charge Movement, Excitation-contraction Coupling, Muscle, Sarcoplasmic Reticulum


Research Summary

Calcium ions play an important role in intracellular communication in many cells. In vertebrate twitch muscle fibers, for example, contraction is normally activated by a depolarization of the membranes of the transverse tubular system. This leads to a movement of calcium ions from inside the sarcoplasmic reticulum (SR), where they are stored, into the myoplasm, where they can bind to the calcium regulatory sites on troponin so that contraction can occur. My research objectives are to understand the factors that control the flow of calcium ions through the calcium channels in the SR membrane (ryanodine receptor protein). These factors include the voltage across the tubular membranes, which is sensed by their voltage sensors (the dihydropyrydine receptors), and free [Ca2+] itself, which can cause calcium-induced calcium release or calcium inactivation of calcium release. Electrophysiological methods are used to monitor currents generated by the voltage sensors, and optical methods are used to monitor the myoplasmic free calcium concentration, which can be used to estimate SR calcium release.

Extensive Research Description

In resting skeletal muscle, calcium ions are stored inside the cell in the sarcoplasmic reticulum (SR). After depolarization of the surface membranes, such as that produced by an action potential, voltage sensors in the transverse tubular membranes (which have been identified with the dihydropyridine receptor protein) activate calcium channels in the SR membrane (which have been identified with the ryanodine receptor protein). This allows calcium ions to move from the SR into the myoplasm where they can bind to the calcium-regulatory sites on troponin to activate contraction. My research interest is to understand how SR calcium release is regulated by the transverse tubular membrane voltage, by calcium, and by other factors. Electrophysiological methods are used to monitor the state of the voltage sensors and optical methods are used to monitor the concentration of myoplasmic free calcium and the amount of calcium released from the SR into the myoplasm


Selected Publications

  • Hollingworth S, Chandler WK, Baylor SM. Effects of tetracaine on voltage-activated calcium sparks in frog intact skeletal muscle fibers. J Gen Physiol, 127:291-307, 2006.
  • Baylor SM, Hollingworth S, Chandler WK. Comparison of simulated and measured sparks in intact skeletal muscle fibers of the frog. J Gen Physiol, 120:349-68, 2002.
  • Hollingworth S, Peet J, Chandler WK, Baylor SM. Calcium sparks in intact skeletal muscle fibers of the frog. J Gen Physiol, 118:653-78, 2001.

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