Regulation of K+ and Ca2+ channels in experimental cardiac failure.
To examine the status of ATP-sensitive K+ (K+ATP) channels and 1,4-dihydropyridine-sensitive Ca2+ (Ca2+DHP) channels during experimental cardiac failure, we have measured the radioligand binding properties of [3H]glyburide and [3H]PN 200 110, respectively, in tissue homogenates from the rat cardiac left ventricle, right ventricle, and brain 4 wk after myocardial infarction induced by left coronary artery ligation. The maximal values (Bmax) for [3H]glyburide and [3H]PN 200 110 binding were reduced by 39 and 40%, respectively, in the left ventricle, and these reductions showed a good correlation with the right ventricle-to-body weight ratio in heart-failure rats. The ligand binding affinities were not altered. In the hypertrophied right ventricle, Bmax values for both the ligands were not significantly different when data were normalized to DNA content or right ventricle weights but showed an apparent reduction when normalized to unit protein or tissue weight. Moderate reductions in channel densities were observed also in whole brain homogenates from heart failure rats. Assessment of muscarinic receptors, beta-adrenoceptors and alpha 1-adrenoceptors by [3H]quinuclidinyl benzilate, [3H]dihydroalprenolol, and [3H]prazosin showed reductions in left ventricular muscarinic and beta-adrenoceptor densities but not in alpha 1-adrenoceptor densities, consistent with earlier observations. It is suggested that these changes may in part contribute to the pathology of cardiac failure.
Gopalakrishnan
M
M
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Triggle
D J
DJ
Rutledge
A
A
Kwon
Y W
YW
Bauer
J A
JA
Fung
H L
HL
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D003331:Coronary Vessels / Q000601:surgery; D004095:Dihydropyridines / Q000378:metabolism; D005905:Glyburide / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D017275:Isradipine; D008026:Ligation; D008297:Male; D009929:Organ Size; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D015221:Potassium Channels; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D005905:Glyburide; D017275:Isradipine