Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Abstract

Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (K_Ca) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) K_Ca channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

Keywords: BK channel; channelome; chondrogenesis; ion channel; muscle differentiation; musculoskeletal diseases; osteoarthritis; osteogenesis; progenitor cell.

Figure 1

A model describing ion conductance fluctuations accounting for the oscillation of the membrane potential and intracellular Ca²⁺ concentration in chondrogenic cells. An original record of a transient elevation of the intracellular Ca²⁺ concentration ([Ca²⁺]) in a single chondrogenic cell (as reported previously in [42]) is shown in black. Simultaneous temporal change of the membrane potential (MP) and the relative magnitude of depolarising and hyperpolarising ionic conductances were estimated and are illustrated in blue, red, and green, respectively.

Figure 2

The STRING interaction network for KCNMA1, showing the top 25 interactants. Edge colours are as follows: known interactions: light blue, from curated databases; magenta, experimentally determined; predicted interactions: green, gene neighbourhood; dark blue, gene co-occurrence; others: lime, text-mining; black, co-expression; purple, protein homology.