Regulatory mechanisms of mitochondrial BKCa channels

Channels (Austin). 2021 Dec;15(1):424-437. doi: 10.1080/19336950.2021.1919463.

Abstract

The mitochondrial BKCa channel (mitoBKCa) is a splice variant of plasma membrane BKCa (Maxi-K, BKCa, Slo1, KCa1.1). While a high-resolution structure of mitoBKCa is not available yet, functional and structural studies of the plasma membrane BKCa have provided important clues on the gating of the channel by voltage and Ca2+, as well as the interaction with auxiliary subunits. To date, we know that the control of expression of mitoBKCa, targeting and voltage-sensitivity strongly depends on its association with its regulatory β1-subunit, which overall participate in the control of mitochondrial Ca2+-overload in cardiac myocytes. Moreover, novel regulatory mechanisms of mitoBKCa such as β-subunits and amyloid-β have recently been proposed. However, major basic questions including how the regulatory BKCa-β1-subunit reaches mitochondria and the mechanism through which amyloid-β impairs mitoBKCa channel function remain to be addressed.

Keywords: BKca channels; DEC sequence; Maxi-K channels; Mitochondria; amyloid beta; beta subunits; genetic origin.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits* / genetics
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits* / metabolism
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Mitochondria* / metabolism

Substances

  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Large-Conductance Calcium-Activated Potassium Channels
  • Calcium

Grants and funding

This work was supported by the doctorate fellowship Fundação para a Ciência e a Tecnologia (FCT; SFRH/BD/146484/2019) to Carmen Santana-Calvo; AHA-WSA 15POST22490015 to Enrique Balderas.AHA-WSA: American Heart Association-Western States Affiliate Wills & Trusts; CONACyT EPE-2017291231 to Ana L.Gonzalez-Cota; CONACyT EPE-2016291121 to Ana L. Gonzalez-Cota; UC MEXUS-CONACyT FE-13-248 to Enrique Balderas.