Intracellular H+ and Ca2+ modulation of trypsin-modified ATP-sensitive K+ channels in rabbit ventricular myocytes.
ATP-sensitive K+ current (IK.ATP) channels are thought to play a role in the K+ efflux observed in cardiac ischemia. Intracellular acidosis is a prominent early effect in ischemia; therefore, the effects of acidosis on IK.ATP may have certain pathophysiological implications. Increased intracellular proton concentration (pHi) is known to regulate IK.ATP in frog skeletal muscle by increasing open probability. The pHi effect on IK.ATP is not clearly understood in heart because, unlike frog skeletal muscle, low pHi causes IK.ATP run-down in inside-out patches. This would tend to mask any opening effect of low pHi if it exists. Trypsin modification of IK.ATP has recently been shown to prevent run-down in inside-out patches. We used single channel recordings in inside-out patches to study IK.ATP after exposure to trypsin. After trypsin treatment, the open probability of IK.ATP was not sensitive to pHi in the absence of ATP. In the presence of ATP, however, a decrease in pHi consistently increased the open probability of trypsin-modified IK.ATP by reducing ATP inhibition. In the absence of ATP the mean open probability was 0.43 +/- 0.07 at pHi 7.4, and 0.5 mM ATP decreased the mean open probability to 0.03 +/- 0.04 at pHi 7.4, but mean open probability was significantly increased to 0.20 +/- 0.07 at pHi 6.3 (n = 7, p < 0.01). Ca2+ did not affect the activity of trypsin-modified IK.ATP in either the absence or presence of ATP at pHi 7.4. However, Ca2+ was able to antagonize the low pHi effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Fan
Z
Z
Cardiac Electrophysiology Laboratories, University of Chicago, IL 60637.
Makielski
J C
JC
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011522:Protons; D011817:Rabbits; D014357:Trypsin
D015221:Potassium Channels; D011522:Protons; D000255:Adenosine Triphosphate; D014357:Trypsin; D002118:Calcium