The cardiac muscle session chaired by Dr. Solaro and brought to the limelight the new key players of muscle contraction. A key observation also included the animal model systems and whole heart studies in vivo, ex vivo and in vitro done to understand the cardiomyopthies in totality as studies traversed from whole heart to the single molecules step by step. Hence, I enumerate contractile players who are in the focus and models of the same.
Beta -MHC - Myosin Heavy Chain (220 Kda) occurs in two isoforms in the heart - the alpha MHC and the beta MHC. As the transition from a non-failing to failing heart progresses, the beta MHC isoform takes over and is predominant in the heart. This isoform is slower than the alpha MHC and thus more energetically economical for the heart. Given the energy starved status of the heart, the switch takes over. The human isoform to begin with is predominantly beta. However, in small rodents like mice alpha isoform is predominant. Dr. Susan Lowey highlighted how a single mutation in MHC can severely affect the kinetics of cross bridge cycling in the herat and lead to cardiomyopathies. It is important to keep in mind here that even after PTU treatment of mouse hearts which would convert alpha to beta MHC - the kinetics of contraction are not the same as that found in higher mammals where the beta isoform is always predominant. Hence the need to study higher models like Guinea pigs, rabbits, pigs is very important. My own work in Dr. De Tombe's lab is targeting this issue as I have developed a Guinea pig model of Heart failure.
MyBP-C - Myosin Binding Protein C is a 140 Kda protein found in the contractile apparatus. MyBP-C puts a constraint on the mysoin heads as they bind of actin and regulates the contraction process. In KO models of MyBP-C cardiomyoptahies are known to develop. Dr. Richard Moss gave a very comprehensive talk on the phosphorylation states of the molecule and how they affect the kinetics of cross-bridge cycling. Dr. Sakthivel Saddyappan has worked on various KO mouse models of this protein and shown how important it is in maintaining the physiological function of the heart. Dr. Moss elegantly showed how phosphorylation of MyBP-C alters the kinetics of contraction in the cardiac muscle.
Titin - The next molecule brought into focus was Titin - a 400 KDa protein. Titin provides a 3 spring system in the contractile machinery to modulate the stiffness of the molecule. Dr. Henk Granzier talked about the how various isoforms of titin alter the passive stiffness of muscle. Dr. Wolfgang Linkes work on the phosphorylation of isoforms of titin by PKG complements the studies shown by Dr. Henk Granzier. In the failing heart a switch takes place from the N2B isoform to the fetal isform N2BA and as this artio alters so does the passive stiffness of the cardiac muscle, leading to impaired relaxation and diastolic failure. Also was shown how PKA and PKC induced phosphorylation of titin alters the passive stiffness.
Also in limelight is Nebulin - the measurement ruler in the muscle, the SERCA pump and Phospholamban system (Dr. Beata Wolska gave a very elegant talk on the workings of the system) which regulate the calcium concentration within the muscle and the Troponin complex - which regulates contraction.