Biomaterial Database

Blockade of 2,4-dinitrophenol induced ATP sensitive potassium current in guinea pig ventricular myocytes by class I antiarrhythmic drugs. 1992

B Wu, and T Sato, and T Kiyosue, and M Arita

Department of Physiology, Oita Medical University, Japan.

OBJECTIVE The aim was to assess the effects of various antiarrhythmic drugs on 2,4-dinitrophenol (DNP) induced outward current (IDNP), presumably the ATP sensitive K+ current (IK,ATP) of isolated cardiac cells and to discuss mechanisms involved in the hypoglycaemia which occurs in patients on these drugs. METHODS The quasi-steady state current-voltage relationship from the isolated guinea pig ventricular cells was measured using whole cell voltage clamp techniques with a ramp pulse programme. The effects of seven different antiarrhythmic drugs on IDNP were examined. Action potentials were elicited at a rate of 0.2 Hz by an intracellular current injection. RESULTS DNP (50 mumol.litre-1) increased the quasi-steady state outward current at potentials positive to about -60 mV. This current (IDNP) was completely inhibited by the subsequent application of glibenclamide (1 mumol.litre-1), thereby suggesting that the IDNP is probably IK,ATP. Cibenzoline (10 mumol.litre-1, class Ia), disopyramide (30 mumol.litre-1, class Ia), and procainamide (100 mumol.litre-1, class Ia) significantly inhibited the IDNP by 95.5(SD 11.3)%, 77.8(21.2)%, and 76.4(23.9)% respectively. Flecainide (class 1c) inhibited the IDNP by 66.9(23.9)% at 10 mumol.litre-1 but not at 2 mumol.litre-1. Mexiletine (30 mumol.litre-1, class Ib), pilsicainide (50 mumol.litre-1, class Ic), and E4031 (10 mumol.litre-1, class III) at concentrations as high as approximately fivefold the clinically effective blood levels, did not suppress IDNP. Except for 10 mumol.litre-1 flecainide, all the concentrations listed above which blocked IDNP were within twofold of the clinical blood concentrations documented to be effective for suppression of arrhythmias. Cibenzoline, disopyramide, and procainamide, but not flecainide, belong to class Ia antiarrhythmic drugs. All these class Ia antiarrhythmic drugs "shortened" the action potential duration of guinea pig ventricular cells, an opposite change to that noted for multicellular preparations, eg, guinea pig papillary muscles. CONCLUSIONS Class Ia antiarrhythmic drugs (cibenzoline, disopyramide, and procainamide) inhibit IDNP (presumably IK,ATP) in guinea pig ventricular cells within a range of therapeutic concentrations. This inhibitory effect of IK,ATP can probably explain the hypoglycaemia which occurs in some patients receiving these drugs, and the prolongation of the action potential duration alleged to occur in "superfused" papillary muscles.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008012	Lidocaine	A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.	Lignocaine,2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide,2-2EtN-2MePhAcN,Dalcaine,Lidocaine Carbonate,Lidocaine Carbonate (2:1),Lidocaine Hydrocarbonate,Lidocaine Hydrochloride,Lidocaine Monoacetate,Lidocaine Monohydrochloride,Lidocaine Monohydrochloride, Monohydrate,Lidocaine Sulfate (1:1),Octocaine,Xylesthesin,Xylocaine,Xylocitin,Xyloneural
D008801	Mexiletine	Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.	KO-1173,KO1173,KOE-1173,Mexiletene,Mexiletine Hydrochloride,Mexitil,Mexitil PL,Mexityl,Novo-Mexiletine,KO 1173,KOE 1173,KOE1173,Novo Mexiletine
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010880	Piperidines	A family of hexahydropyridines.
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011342	Procainamide	A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.	Procaine Amide,Apo-Procainamide,Biocoryl,Novocainamide,Novocamid,Procainamide Hydrochloride,Procamide,Procan,Procan SR,Procanbid,Pronestyl,Rhythmin,Amide, Procaine,Hydrochloride, Procainamide
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004140	Dinitrophenols	Organic compounds that contain two nitro groups attached to a phenol.
D004206	Disopyramide	A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.	Diisopyramide,Disopyramide Monohydrochloride,Disopyramide Phosphate,Disopyramide Phosphate (1:1),Disopyramide Phosphate (1:1), (+-)-Isomer,Disopyramide Phosphate (1:1), (R)-Isomer,Disopyramide Phosphate (1:1), (S)-Isomer,Disopyramide, (+-)-Isomer,Disopyramide, (R)-Isomer,Disopyramide, (S)-Isomer,Disopyramide, D-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:1), (R)-Isomer,Disopyramide, L-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:2), (+-)-Isomer,Disopyramide, L-Tartrate, (S)-isomer,Norpace,Palpitin,Palpitine,Rhythmodan,Ritmilen,Rythmilen,SC-13957,SC 13957,SC13957