Isoflurane decreases ATP sensitivity of guinea pig cardiac sarcolemmal KATP channel at reduced intracellular pH. Anesthesiology 2003 Feb;98(2):396-403
Date
01/29/2003Pubmed ID
12552199DOI
10.1097/00000542-200302000-00020Scopus ID
2-s2.0-0037317432 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND: Volatile anesthetics can protect the myocardium against ischemic injury by opening the adenosine triphosphate (ATP)-sensitive potassium (K(atp)) channels. However, direct evidence for anesthetic-channel interaction is still limited, and little is known about the role K(atp) channel modulators play in this effect. Because pH is one of the regulators of K(atp) channels, the authors tested the hypothesis that intracellular pH (pHi) modulates the direct interaction of isoflurane with the cardiac K(atp) channel.
METHODS: The effects of isoflurane on sarcolemmal K(atp) channels were investigated at pHi 7.4 and pHi 6.8 in excised inside-out membrane patches from ventricular myocytes of guinea pig hearts.
RESULTS: At pHi 7.4, intracellular ATP (1-1,000 microm) inhibited K(atp) channels and decreased channel open probability (Po) in a concentration-dependent manner with an IC(50) of 8 +/- 1.5 microm, and isoflurane (0.5 mm) either had no effect or decreased channel activity. Lowering pHi from 7.4 to 6.8 enhanced channel opening by increasing Po and reduced channel sensitivity to ATP, with IC shifting from 8 +/- 1.2 to 45 +/- 5.6 microm. When applied to the channels activated at pHi 6.8, isoflurane (0.5 mm) increased Po and further reduced ATP sensitivity, shifting IC(50) to 110 +/- 10.0 microm.
CONCLUSIONS: Changes in pHi appear to modulate isoflurane interaction with the cardiac K(atp) channel. At pHi 6.8, which itself facilitates channel opening, isoflurane enhances channel activity by increasing Po and reduces sensitivity to inhibition by ATP without changing the unitary amplitude of single channel current or the conductance. These results support the hypothesis of direct isoflurane-K(atp) channel interaction that may play a role in cardioprotection by volatile anesthetics.
Author List
Stadnicka A, Bosnjak ZJMESH terms used to index this publication - Major topics in bold
ATP-Binding Cassette TransportersAdenosine Triphosphate
Anesthetics, Inhalation
Animals
Cell Separation
Depression, Chemical
Guinea Pigs
Hydrogen-Ion Concentration
In Vitro Techniques
Isoflurane
KATP Channels
Myocardium
Patch-Clamp Techniques
Potassium
Potassium Channels
Potassium Channels, Inwardly Rectifying
Sarcolemma
