State-dependent modification of ATP-sensitive K+ channels by phosphatidylinositol 4,5-bisphosphate.
With inside-out patch recordings in ventricular myocytes from the hearts of guinea pigs, we studied ATP-sensitive K+ (K(ATP)) channels activated by phosphatidylinositol 4,5-bisphosphate (PIP2) with respect to sensitivity to ATP when in either a rundown state (RS) or a non-rundown state (NRS). Rundown of K(ATP) channels was induced by exposure either to ATP-free solution or to ATP-free solution containing 19 microM Ca2+. Exposure of membrane patches to 10 microM PIP2 reactivated channels with both types of rundown. The reactivation by PIP2 did not require ATP in the bath. The IC50 of channels recovered from RS and before the rundown was 37.1 and 31.1 microM, respectively. PIP2 irreversibly increased the mean current when the channel was in the NRS. This was associated with a shift of IC50 to 250.6 microM after PIP2 exposure. PIP2 activates NRS K(ATP) channels by decreasing their sensitivity to ATP, whereas PIP2 reactivates RS-K(ATP) channels independently of ATP without changing ATP sensitivity.
Okamura
M
M
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan.
Kakei
M
M
Ichinari
K
K
Miyamura
A
A
Oketani
N
N
Koriyama
N
N
Tei
C
C
D000255:Adenosine Triphosphate / Q000172:deficiency / Q000494:pharmacology*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D016276:Ventricular Function
D007004:Hypoglycemic Agents; D019269:Phosphatidylinositol 4,5-Diphosphate; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D002122:Calcium Chloride; D005905:Glyburide