@article{oai:niigata-u.repo.nii.ac.jp:00014802,
 author = {畑田, 勝治},
 issue = {7},
 journal = {新潟医学会雑誌, 新潟医学会雑誌},
 month = {Jul},
 note = {BACKGROUND：Tumor necrosis factor-α (TNF-α) is an essential mediator of cardiovascular changes observed during the bacterial sepsis, myocardial infarction, and heart failure and it decreases myocardial contractility. However, its electrophysiological property is unknown. We here report that TNF-α inhibits cardiac delayed rectifier pottasium current (IK). METHOD：Ventricular myocytes isolated from guinea pig hearts were voltage-clamped by conventional whole-cell mode (34-36℃). Amplitudes of tail and steady-state (2s pulse) currents were measured as IK. Intrapippete and extracellular K concentrations are 150 mM (pCa＝8) and 5.4 mM, respectively. To minimize L-type Ca currents, nisoldipine (2μM) was usually added to extracellular solution. RESULTS：TNF-α suppressed the IK by 98.4±1.9% that had been enhanced to ～2-fold by isoproterenol (ISO；20nM), although it did not affect the basal IK. The action was dose-dependent with IC50 of 11.6±0.69 ng/ml (n＝23). TNF-α antagonized histamine- and forskolin-enhanced IK (n＝4), but failed to inhibit that enhanced by internal application of cyclic AMP (n＝4). Preincubation of myocytes with PTX (5μg/ml for>120 min) abolished the inhibitory action of TNF- α on ISO-enhanced IK(n=4). Preincubation of myocytes with N-oleoylethanolamine (NOE) ceramidase inhibitor, abolished the inhibitory action of TNF-α on ISO-enhanced IK (n=4), and C_2-ceramic inhibited ISO-enhanced IK as well as TNF-α did. CONCLUSION: TNF-α inhibited IK in a dose-dependent manner by modulating cAMP concentration, and PYX-sensitive G protein and sphingomyelin pathway were concerned with the inhibitory action on ISO-enhanced IK. Under pathological conditions, TNF-αmay prolong the action potential duration, thereby leads to intracellular Ca overload.},
 pages = {306--317},
 title = {Tumor necrosis factor-αによるモルモット心室筋遅延整流性カリウム電流の抑制},
 volume = {115},
 year = {2001}
}