ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats.
Hypoxia-induced shortening of the action potential duration, attributed to activation of the ATP-sensitive potassium (KATP) channels, occurs to a much greater extent in ventricular cells from diabetic rats. This study examined whether the KATP channels are altered in streptozotocin-diabetic myocardium. In inside-out patches from ventricular myocytes (with symmetrical 140 mM [K+]), inward KATP currents (at potentials negative to the K+ reversal potential) were similar in amplitude in control and diabetic patches (slope conductances: 69 and 74 pS, respectively). However, outward single-channel currents were larger for channels from diabetic heart cells than from control cells (e.g., at +75 mV the diabetic channel currents were 3.7 +/- 0.3 pA vs. 2.7 +/- 0.1 pA for control currents, p < 0.05), due to reduced inward rectification of diabetic channel currents. There was no difference in open and closed times between control and diabetic channels. The IC50 for ATP inhibition of the KATP channel single-channel currents was 11.4 microM for control currents and 4.7 microM for diabetic channel currents. Thus, the major difference found between KATP channels from control and diabetic hearts was the greater outward diabetic single-channel current, which may contribute to the enhanced sensitivity to hypoxia (or ischemia) in diabetic hearts.
Smith
J M
JM
Department of Physiology, Midwestern University, Downers Grove, IL. 60515, USA.
Wahler
G M
GM
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004594:Electrophysiology; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020110:Pinacidil; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate