Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Query: UMLS:C0848283 (
rundown
)
502
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phosphatidylinositol 4,5-bisphosphate (PIP
2
) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP
2
sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP
2
remains unclear. Here, we investigate the effects of PIP
2
on Kv2.1 channels by applying exogenous PIP
2
to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP
2
using a rapamycin-translocated 5-phosphatase (
FKBP
-Inp54p). Exogenous PIP
2
rescued Kv2.1 channels from
rundown
and partially prevented the shift in the voltage-dependence of inactivation observed in inside-out patch recordings. Native PIP
2
depletion by the recruitment of
FKBP
-Insp54P or M1R activation in whole-cell experiments, induced a shift in the voltage-dependence of inactivation, an acceleration of the closed-state inactivation, and a delayed recovery of channels from inactivation. No significant effects were observed on the activation mechanism by any of these treatments. Our data can be modeled by a 13-state allosteric model that takes into account that PIP
2
depletion facilitates inactivation of Kv2.1. We propose that PIP
2
regulates Kv2.1 channels by interfering with the inactivation mechanism.
...
PMID:Regulation of Kv2.1 channel inactivation by phosphatidylinositol 4,5-bisphosphate. 2937 18
