Molecular mechanisms and physiological relevance of RGK proteins in the heart

Acta Physiol (Oxf). 2018 Apr;222(4):e13016. doi: 10.1111/apha.13016. Epub 2017 Dec 29.


The primary route of Ca2+ entry into cardiac myocytes is via 1,4-dihydropyridine-sensitive, voltage-gated L-type Ca2+ channels. Ca2+ influx through these channels influences duration of action potential and engages excitation-contraction (EC) coupling in both the atria and the myocardium. Members of the RGK (Rad, Rem, Rem2 and Gem/Kir) family of small GTP-binding proteins are potent, endogenously expressed inhibitors of cardiac L-type channels. Although much work has focused on the molecular mechanisms by which RGK proteins inhibit the CaV 1.2 and CaV 1.3 L-type channel isoforms that expressed in the heart, their impact on greater cardiac function is only beginning to come into focus. In this review, we summarize recent findings regarding the influence of RGK proteins on normal cardiac physiology and the pathological consequences of aberrant RGK activity.

Keywords: CaV1.2; L-type; RGK protein; Rad; Rem; α1C.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism*
  • Myocytes, Cardiac / metabolism*


  • Monomeric GTP-Binding Proteins