Alinidine as a model of the mode of action of specific bradycardic agents on SA node activity.
Three different bradycardic agents, alinidine, AQ-A39 and UL-FS49 increase the intrinsic cycle length of the isolated SA node preparation of the rabbit. This increase is mainly caused by a decrease in rate of diastolic depolarization. One of these agents, alinidine, was used to study the underlying ionic mechanism of the decrease in the diastolic depolarization rate in isolated cells and small cell clusters of the rabbit SA node. In these preparations alinidine slowed down the rate of spontaneous activity at higher concentrations (80 microM). At lower concentrations (10 microM) the decrease in rate of spontaneous activity was variable, but injection of a hyperpolarizing current slowed the spontaneous rate more in the presence of alinidine, indicating an increase in membrane resistance. In voltage clamp experiments we found that the main effect of alinidine was a block of the hyperpolarization activated current if. The block was potential dependent and was maximal in the potential range in which diastolic depolarization occurs. These results are discussed in relation to previous findings of others.
van Ginneken
A C
AC
Department of Physiology, Academic Medical Centre, Amsterdam, The Netherlands.
Bouman
L N
LN
Jongsma
H J
HJ
Duivenvoorden
J J
JJ
Opthof
T
T
Giles
W R
WR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D054833:Isoindoles; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010797:Phthalimides / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D054833:Isoindoles; D010797:Phthalimides; C022192:alinidine; D003000:Clonidine; C030532:falipamil; C043636:zatebradine