Thermoregulation without the set point: roles of TRP Channels

Abstract

protein kinase II (CaMKII). Conversely, failing myocytes that harbor increased amount of truncated TrkB (with limited tyrosine kinase activity) and chronically activated CaMKII are almost insensitive to BDNF. Thus, BDNF/TrkB signaling provides a novel pathway by which the peripheral nervous system directly and tonically influences myocardial function, in parallel with β-adrenergic control. Our data provide a mechanistic basis to recent clinical observations showing that lower levels of circulating BDNF correlate with worsening of function in heart failure patients, particularly under exercise conditions. Moreover, they concur to explain why tyrosine kinase inhibitors, used especially to treat certain forms of breast cancer, can directly impair systolic and diastolic function. In essence, alterations in BDNF/TrkB signaling are likely new contributors to acute and chronic cardiac affections.