Fibroblast Growth Factor Homologous Factors Modulate Cardiac Sodium and Calcium Channels
© 2018 Elsevier Inc. All rights reserved. Fibroblast growth factor homologous factors (FHFs) are a noncanonical subset of intracellular fibroblast growth factors that do not function as growth factors but have been implicated in a variety of biological processes and in disease. In the heart, they regulate the voltage-gated Na+ channel (NaV1.5) and the main voltage-gated Ca2+ channel (CaV1.2). FHFs interact directly with NaV1.5, but how they regulate CaV1.2 is less clear. A mutation in the predominant human cardiac FHF that perturbs NaV1.5 interaction and causes channel dysfunction has been linked to Brugada syndrome. Moreover, a mutation in NaV1.5 that affects FHF interaction has been associated with an inherited arrhythmia syndrome. The lack of a knockout mouse model previously hampered our understanding of the integrated effects of FHFs on cardiac ion channel function, but recent advances have provided new tools that promise to greatly enhance our comprehension. As these new models are poised to provide novel insights, I will discuss here the current knowledge of FHFs in cardiac function and forecast the questions that will now be addressed with the development of new tools.
- Cardiac Electrophysiology: From Cell to Bedside: Seventh Edition
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International Standard Book Number 13 (ISBN-13)
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