[Stimulus-dependent blockade of the Na channels of isolated myocardial cells in the rat by the anti-arrhythmia agent N-propyl ajmaline (neogiluritmal)].
The patch-clamp method was used to study the effect of N-propyl ajmaline (NPA) on sodium currents (INa) in enzymatically isolated cells of adult rats. When applied at concentrations of 10(-5)--2 X 10(-5) M NPA produced a use-dependent inhibition of INa. The rate and depth of this blockade increased with NPA concentration, frequency and magnitude of depolarizing pulses. Voltage dependence of the blockade was revealed beyond the potential range where the fraction of activated Na channels was close to 1.0. Turning on the strong hyperpolarizing prepulse (100-ms duration) before each test pulse induced a prompt increase of INa (due to the removal of resting inactivation) which declined pulse by pulse during subsequent repetitive stimulation. A single long-lasting (3000 ms) depolarizing step, in contrast to the train of short (5 ms) depolarizing pulses did not enhance appreciably the blocking action of NPA. From an analysis of the data obtained it was inferred that NPA inhibits INa due to a voltage-dependent interaction with open Na channels. It is emphasized that NPA has similar blocking effects on Na channels in myocardial cells and nerve fibers.
D000404:Ajmaline / Q000031:analogs & derivatives*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011219:Prajmaline / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D000404:Ajmaline; D011219:Prajmaline; D012964:Sodium
Stimulzavisimaia blokada Na-kanalov izolirovannykh kletok miokarda krysy antiaritmikom N-propil-aĭmalinom (neogiluritmalem).