Electrostatic interaction of internal Mg2+ with membrane PIP2 Seen with KCNQ K+ channels.
J Gen Physiol
; 130(3): 241-56, 2007 Sep.
Article
en En
| MEDLINE
| ID: mdl-17724161
ABSTRACT
Activity of KCNQ (Kv7) channels requires binding of phosphatidylinositol 4,5-bisphosphate (PIP(2)) from the plasma membrane. We give evidence that Mg(2+) and polyamines weaken the KCNQ channel-phospholipid interaction. Lowering internal Mg(2+) augmented inward and outward KCNQ currents symmetrically, and raising Mg(2+) reduced currents symmetrically. Polyvalent organic cations added to the pipette solution had similar effects. Their potency sequence followed the number of positive charges putrescine (+2) < spermidine (+3) < spermine (+4) < neomycin (+6) < polylysine (>>+6). The inhibitory effects of Mg(2+) were reversible with sequential whole-cell patching. Internal tetraethylammonium ion (TEA) gave classical voltage-dependent block of the pore with changes of the time course of K(+) currents. The effect of polyvalent cations was simpler, symmetric, and without changes of current time course. Overexpression of phosphatidylinositol 4-phosphate 5-kinase Igamma to accelerate synthesis of PIP(2) attenuated the sensitivity to polyvalent cations. We suggest that Mg(2+) and other polycations reduce the currents by electrostatic binding to the negative charges of PIP(2), competitively reducing the amount of free PIP(2) available for interaction with channels. The dose-response curves could be modeled by a competition model that reduces the pool of free PIP(2). This mechanism is likely to modulate many other PIP(2)-dependent ion channels and cellular processes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poliaminas
/
Potasio
/
Activación del Canal Iónico
/
Membrana Celular
/
Fosfatidilinositol 4,5-Difosfato
/
Canal de Potasio KCNQ2
/
Canal de Potasio KCNQ3
/
Magnesio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Gen Physiol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos