Department of Internal Medicine
Cardiovascular Division
Research Opportunities


Christopher Rembold, MD
Regulation of Smooth Muscle Contraction

The Rembold laboratory has been studying the mechanisms responsible for arterial smooth muscle contraction and relaxation since 1987.  The most accepted mechanism for smooth muscle contraction is via increased intracellular calcium resulting in increased myosin phosphorylation.  Relaxation is typically thought to be the reversal of activation, i.e. deactivation, which is caused by a reduction in intracellular calcium and myosin phosphorylation.  Recently, we have concentrated on two mechanisms that do not involved regulation by myosin phosphorylation.
  • Recent studies in tracheal smooth muscle suggest that the actin cytoskeleton is plastic during contraction.  We find an increase in actin polymerization during the sustained phase of contraction.  We are currently evaluating whether stimulus induced changes in paxillin phosphorylation, actin polymerization, and the resulting change in tissue rheology are important in the regulation of force.  Studies involve biochemical and biophysical measures (noise temperature). 

  • There is also a novel form of smooth muscle relaxation that does not involve deactivation mechanisms. We found that that elevations in cGMP and cAMP caused a relaxation elevated myosin phosphorylation. This process was termed force suppression.  We found that force suppression was associated with phosphorylation of the small heat shock protein known as HSP20 (aka P20 or HSPB6). A peptide of HSP20 has a sequence homology with troponin I, the main regulatory protein in skeletal and cardiac muscle. This peptide binds thin filaments, reduces myosin ATPase activity, and relaxes skinned swine carotid artery.  We are currently testing the hypothesis that binding of phosphorylated HSP20 to the smooth muscle thin filaments may turn off thin filaments so that phosphorylated myosin does not interact with the thin filament (i.e. a model similar to skeletal muscle troponin I).

Dr. Rembold is also researching sleep apnea in children and the use of carotid intimal medial thickness in the detection of preclinical atherosclerosis.

Selected Publications

Rembold C.M., Foster, B., Strauss, J., Wingard, C., Van Eyk, J.E. cGMP mediated phosphorylation of heat shock protein 20 may cause smooth muscle relaxation without myosin light chain dephosphorylation. Journal of Physiology (London), 524:865-878, 2000.

Rembold C.M., Wardle, R.M., Wingard, C.J., Batts, T.W., Etter, E.F., Murphy, R.A.  Cooperative attachment of crossbridges predicts regulation of smooth muscle force by myosin phosphorylation.  American Journal of Physiology (Cell Physiology), 287:C594-C602, 2004

Meeks, M., Ripley, M., Jin, Z. Rembold C.M.,   Heat shock protein 20 mediated force suppression in forskolin relaxed swine carotid artery.  Am J Physiology Cell Physiology,  288:C633-C639, 2005.

Suratt, P.M., Barth, J.T., Diamond, R., D'Andrea, L., Nikova, M., Periello, V.A., Carskadon, M.A., Rembold, C.M.  Reduced Time in Bed and Obstructive Sleep Disordered Breathing in Children are Associated with Cognitive Impairment.  Pediatrics, 119:320-329, 2007.

Rembold, C.M.  Force suppression and the crossbridge cycle in swine carotid artery.  American Journal of Physiology Cell Physiology, 293:1003-1009, 2007.

Rembold, C.M., Tejani, A,D. Ripley, M.L., Han, S.  Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction.  American Journal of Physiology Cell Physiology, 293:993-1002, 2007.

Stein, J.H., Korcatz, C.E., Hurst, R.T., Lonn, E., Kendall, C.B., Mohler, E.R., Naijar, S.S. Rembold, C.M., Post, W.S.  Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: A consensus statement from the American society of echocardiography carotid intima-media thickness task force endorsed by the society for vascular medicine.  Journal of the American Society of Echocardiography, 21:93-111, 2008.