Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

A large-conductance (BK) potassium channel subtype affects both growth and mineralization of human osteoblasts

Henney, Neil Colin, Li, Bo, Elford, Carol, Reviriego, Pablo, Campbell, Anthony Keith, Wann, Kenneth Taylor and Evans, Bronwen Alice James ORCID: https://orcid.org/0000-0002-3082-1008 2009. A large-conductance (BK) potassium channel subtype affects both growth and mineralization of human osteoblasts. American Journal of Physiology - Cell Physiology 297 (6) , C1397-C1408. 10.1152/ajpcell.00311.2009

Full text not available from this repository.

Abstract

The pharmacology of the large-conductance K+ (BK) channel in human osteoblasts is not well defined, and its role in bone is speculative. Here we assess BK channel properties in MG63 cells and primary human osteoblasts and determine whether pharmacological modulation affects cell function. We used RT-PCR and patch-clamp methods to determine the expression of BK channel subunits and cell number assays in the absence and presence of BK channel modulators. RT-PCR showed the presence of KCNMA1, KCNMB1, KCNMB2, KCNMB3, and KCNMB4 subunits. The BK channel was voltage dependent, with a mean unitary conductance of 228.8 pS (n = 10) in cell-attached patches (140 mM K+/140 mM K+) and a conductance of 142.5 pS (n = 16) in excised outside-out and 155 pS (n = 6) in inside-out patches in 3 mM K+/140 mM K+. The selectivity ratio (ratio of K+ to Na+ permeability) was 15:1. The channel was blocked by tetraethylammonium (TEA, 0.3 mM), iberiotoxin (5–60 nM), tetrandrine (5–30 μM), and paxilline (10 μM) and activated by isopimaric acid (20 μM). BK channel modulators affected MG63 cell numbers: TEA and tetrandrine significantly increased cell numbers at low concentrations (3 mM and 3 μM, respectively) and reduced cell numbers at higher concentrations (>10 mM and >10 μM, respectively). Neither iberiotoxin (20–300 nM) nor slotoxin (300 nM) affected cell numbers. The increase in cell numbers by TEA was blocked by isopimaric acid. TEA (0.1–3.0 mM) significantly increased mineralization in primary osteoblasts. In conclusion, the BK channel has a distinctive pharmacology and is thus a target for therapeutic strategies aimed at modulating osteoblast proliferation and function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Pharmacy
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: MG63 cells; bone; potassium current; tetrandrine
Publisher: American Physiological Society
ISSN: 0363-6143
Last Modified: 17 Oct 2022 10:01
URI: https://orca.cardiff.ac.uk/id/eprint/6560

Citation Data

Cited 39 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item