Aprikalim reduces the Na+-Ca2+ exchange outward current enhanced by hyperkalemia in rat ventricular myocytes.
BACKGROUND
[corrected] Aprikalim, an adenosine triphosphate (ATP) sensitive K+ (K(ATP)) channel opener, attenuates the elevation of intracellular Ca2+ concentration ([Ca2+]i) and improves the contractile functions after hyperkalemic and hypothermic cardioplegia. There is evidence that cardioplegia increases the Na+-Ca2+ exchange activity without affecting Ca2+ influx through L-type Ca2+ channels or Ca2+ content in the sarcoplasmic reticulum, the intracellular Ca2+ store.


METHODS
We measured the Na+-Ca2+ exchange outward current with the patch-clamp technique in single rat ventricular myocytes exposed to hyperkalemia and hypothermia in the presence of aprikalim. The intracellular calcium concentration ([Ca2+]i) during cardioplegia, and the contractile function and [Ca2+]i transients induced by electrical stimulation or caffeine during rewarming and reperfusion in single ventricular myocytes were also determined. Contraction and [Ca2+]i were determined with video tracking and spectrofluorometry, respectively.


RESULTS
Aprikalim, 100 micromol/L, the effect of which was blocked by glibamclamide, a K(ATP) inhibitor, significantly attenuated the hyperkalemia-elevated Na+-Ca2+ exchange current by 26% and 11% at 22 degrees C and 4 degrees C, respectively. Aprikalim also attenuated significantly the [Ca2+]i elevated during cardioplegia. Furthermore aprikalim significantly attenuated the reduction in amplitude and prolongation in duration of contraction of myocytes after cardioplegia. The effects of aprikalim mimicked those of nickle (Ni2+), a Na+-Ca2+ exchange blocker. The electrically or caffeine-induced [Ca2+]i transients were unaltered by cardioplegia or aprikalim.


CONCLUSIONS
Aprikalim attenuates the Na+-Ca2+ exchange outward current elevated by hyperkalemia, which may attenuate the [Ca2+]i elevation during hyperkalemia and improve the contractile function after cardioplegia in the ventricular myocyte. The study provides further support that addition of a K(ATP) channel opener to the cardioplegic solution may produce beneficial effects in open heart surgery.
Li
Hong-Yu
HY
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
Wu
Song
S
He
Guo-Wei
GW
Wong
Tak-Ming
TM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006352:Heart Ventricles / Q000166:cytology*; D006947:Hyperkalemia / Q000378:metabolism*; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010847:Picolines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*
D010847:Picolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; D019831:Sodium-Calcium Exchanger; C061043:aprikalim; D009532:Nickel; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium