SLO2 Channels Are Inhibited by All Divalent Cations That Activate SLO1 K+ Channels.
J Biol Chem
; 291(14): 7347-56, 2016 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-26823461
ABSTRACT
Two members of the family of high conductance K(+)channels SLO1 and SLO2 are both activated by intracellular cations. However, SLO1 is activated by Ca(2+)and other divalent cations, while SLO2 (Slack or SLO2.2 from rat) is activated by Na(+) Curiously though, we found that SLO2.2 is inhibited by all divalent cations that activate SLO1, with Zn(2+)being the most effective inhibitor with an IC50of â¼8 µmin contrast to Mg(2+), the least effective, with an IC50of â¼ 1.5 mm Our results suggest that divalent cations are not SLO2 pore blockers, but rather inhibit channel activity by an allosteric modification of channel gating. By site-directed mutagenesis we show that a histidine residue (His-347) downstream of S6 reduces inhibition by divalent cations. An analogous His residue present in some CNG channels is an inhibitory cation binding site. To investigate whether inhibition by divalent cations is conserved in an invertebrate SLO2 channel we cloned the SLO2 channel fromDrosophila(dSLO2) and compared its properties to those of rat SLO2.2. We found that, like rat SLO2.2, dSLO2 was also activated by Na(+)and inhibited by divalent cations. Inhibition of SLO2 channels in mammals andDrosophilaby divalent cations that have second messenger functions may reflect the physiological regulation of these channels by one or more of these ions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Zinco
/
Cátions Bivalentes
/
Proteínas de Drosophila
/
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta
/
Magnésio
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article