Inhibition by agmatine on spontaneous activity of rabbit atrioventricular node cells.
OBJECTIVE
To study the effects of agmatine on spontaneous activity of atrioventricular (AV) node and its action mechanisms.


METHODS
Action potentials in AV node cells were recorded using intracellular microelectrode technique.


RESULTS
Agmatine not only reduced the amplitude of action potential (APA), maximal rate of depolarization (Vmax), velocity of diastolic (phase 4) depolarization (VDD), and rate of spontaneous firing (RSF), but also prolonged 90% duration of action potential (APD90) in a concentration-dependent manner. The effects of agmatine (10 mmol/L) could be blocked completely by pretreatment with idazoxan (0.1 mmol/L), an imidazoline receptor (IR) and alpha 2-adrenergic receptor (alpha 2-AR) antagonist. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 0.5 mmol/L), a nitric oxide (NO) synthase inhibitor, did not affect the effects of agmatine on AV node cells. Elevation of Ca2+ concentration (5 mmol/L) in perfusate antagonized the effects of agmatine (10 mmol/L). Lemakalim (30 mumol/L), an ATP-sensitive potassium channel opener, inhibited the prolonging effects of agmatine on repolarization.


CONCLUSIONS
The inhibitory effects of agmatine on spontaneous activity of AV node cells in rabbits were likely mediated by IR and/or alpha 2-AR, and were related to the reduction in calcium influx and potassium efflux.
Li
X T
XT
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Duan
H R
HR
He
R R
RR
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000166:cytology / Q000502:physiology*; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D005260:Female; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000378:metabolism; D011817:Rabbits
D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D000376:Agmatine; D011188:Potassium; D002118:Calcium; D019329:Idazoxan