[Effects of endothelin on the electrical activity of sino-atrial pacemaker cells of rabbit].
The effects of endothelin-1 (ET-1) on the electrophysiological activity of pacemaker cells of rabbit sino-atrial node were examined by using intracellular microelectrode technique. The results obtained were as follows: (1) With superfusion of ET-1 (1-30 nmol/l), the velocity of diastolic depolarization (VDD) of pacemaker cells was significantly decreased in a concentration dependent manner, resulting in a reduced rate of pacemaker firing (RPF). (2) The decreases in RPF and VDD induced by ET-1 could be virtually blocked by pretreatment with ET(A) receptor blocker BQ-123 (20 or 100 micrograms/L). It was strongly suggested that the electrophysiological effects of ET-1 on the pacemaker cells were mediated by the ET(A) receptor. (3) The negative chronotropic action of ET-1 on the pacemaker cells was totally abolished by pretreatment with a kind of KATP channel blocker glibenclamide (10 mumol/L). On the basis of above results, it appears that the binding of ET-1 with ET(A) receptor may induce an activation of KATP channels with resultant increase in K+ current so as to decrease the velocity of diastolic depolarization in the pacemaker cells.
Zhang
Z
Z
Department of Physiology, Hebei Medical University, Shijiazhuang.
Li
Y L
YL
Ho
S Y
SY
D000818:Animals; D004594:Electrophysiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D010456:Peptides, Cyclic / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D026902:Potassium Channel Blockers; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D005905:Glyburide