38-Year-Old Mystery Of The Heart Solved
Researchers are finally offering an explanation of how the function of a key protein in the heart changes in heart failure, according to a new study.
Since 1976 researchers have known the fact that heart regulates its calcium sensitivity by phosphorylating (adding negative phosphate groups) to a key cardiac protein called troponin I. When heart failure occurs, the phosphate groups are removed from troponin. However, it was not known how this caused an increase calcium sensitivity.
Researchers studied the troponin complex with nuclear magnetic resonance (NMR) spectroscopy and found that unphosphorylated troponin I binds to troponin C to keep it in an optimal orientation for triggering contraction. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method that uses superconducting magnets to probe atomic level structure.
"Scientists believed that the dephosphorylation of troponin I seen in heart failure somehow caused the troponin complex to become less functional," said Peter Hwang, lead author in the study, in the press release. "Actually, the change brings it into the optimal alignment to trigger contraction. The heart has other mechanisms of regulating calcium sensitivity that probably also act by stabilizing or disrupting this arrangement."
Hwang hypothesized that the heart continuously adjusts calcium sensitivity in order to maintain a proper balance between contraction and relaxation.
"I believe that calcium sensitivity will become a central concept in cardiology. The increase in calcium sensitivity seen in heart failure may be the heart's response to ongoing volume or pressure overload. While this would be a beneficial compensation in the setting of systolic heart failure, it is probably not helpful in diastolic heart failure. A Heart and Stroke Foundation grant is now allowing our team to develop troponin-targeting drugs that modulate calcium sensitivity for the treatment of heart failure. We will see if this hypothesis is correct."
The study has been detailed in the Proceedings of the National Academy of Sciences.