[Changes in balance of ionic currents of cardiac cells as one of the mechanisms of arrhythmia].
Changes in balance of transmembrane ionic currents were achieved in two ways: 1) modifying Na current with lysophosphatidylcholine (LPC), a toxic metabolite of ischemia; 2) modifying Ca current with BAY K 8644, an agonist of Ca channels. Elementary current through Na channel were recorded in an inside-out mode using patch clamp techniques. The effects of BAY K 8644 were studied on the transmembrane potential of guinea pig papillary muscle (PM) and sheep Purkinje fibers (PF). Application of LPC (9-25 microns) from the inner side of the membrane caused a peak reduction of averaged Na current and prolonged the time of inactivation. Analysis of single channel behavior revealed that LPC induced long-lasting bursts of openings, resulting in a noninactivated fraction of Na current. The duration of the action potential (AP) of PM increased slightly (20%), while PF AP duration increased progressively with time even at a low BAY K 8644 dose (0.5 microM). Early after-depolarization (EAD) occurred at min 5. After 10-minute drug use, PF became inexcitable at high plateau levels. TTX and ethmozine (1 microM) restored AP. Thus, changes in balance of ion c currents by modifying Na and/or Ca channels may culminate in the occurrence of an additional steady-state potential at plateau levels. The latter may result EAD and re-entry around functionally inexcitable PF. The similarity of mechanisms of arrhythmias induced by ischemia using the presented model is discussed.
A I
AI
Undrovinas
N A
NA
Burnashev
I A
IA
Fledervish
K
K
Dzheniuari
I
I
Iuriavichius
Zh
Zh
Ridl
D
D
Zablotskaĭte
Ch
Ch
Siuĭ
L V
LV
Rozenshtraukh
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D015220:Calcium Channels / Q000502:physiology*; D006168:Guinea Pigs; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D010210:Papillary Muscles / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000503:physiopathology*; D012756:Sheep; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors
D015220:Calcium Channels; D008244:Lysophosphatidylcholines; D015222:Sodium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Narushenie balansa ionnykh tokov serdechnykh kletok kak odin iz mekhanizmov aritmiĭ.