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University Professor and Head
Physiology and Biophysics
Integrated molecular structural and cellular biology of cardiac muscle contraction
We want to know the fundamental mechanisms responsible for regulation of the molecular motors of heart muscle cells. These motors are housed in myofilaments responsible for shortening of cardiac muscle cells. Our focus is on the molecular switch that turns on the motor. Our experiments address the following question: What events signal switch function and how is the switch modulated by myofilament structure, chemistry, mechanical state and drugs? We approach this question at several levels of organization by integrating information derived from techniques using the disciplines of biophysics, biochemistry as well as molecular, structural and cellular biology. For example, we have cloned, expressed wild type and mutants of one element in the switch, a protein called troponin I. We exchange native myofilament TnI for the mutants either in vitro or in transgenic animals. We measure force, shortening and energy transduction in the myofilaments and in intact single cells. An important endpoint and success of our approaches has been the development of new drugs for use in the treatment of heart failure.
Recent Publications:
1) Solaro, R.J., Rarick, H.M. Troponin and tropomyosin: Proteins that switch on and tune in the activity of cardiac myofilaments. 1998; Circ. Res. 83:471-480.
2) Solaro, R.J. Invited Editorial: Troponin I, Stunning, Hypertrophy, and Failure of the Heart. Circ. Res. 1999;84:122-124.
3) Solaro, R. J. Is Ca2+ the "cure" for dilated cardiomyopathy? Nature Medicine 1999; 5:1353-54.
4) Solaro RJ. Invited Editorial: Myosin light Chain Phosphatase: A Cinderella of Cellular Signaling. Circ Res. 2000;87:173-175.
5) Arteaga, G.M., Palmiter K.A., Leiden, J.M., Solaro R.J. Attenuation of length-dependent activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I. J Physiol (London) 2000; 526:541-549.