- 作者: Hengtao Zhang Mario Vassalle
- 作者服務機構: Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, HBrooklyn, N.y., USA
- 中文摘要: --
- 英文摘要:
Among the mechanisms proposed for the increase in
discharge of sino-atrial node (SAN) by norepinephrine
(NE) are an increase in the hyperpolarization-activated
current If and in the slow inward current Ica,L. If If is the
primary mechanism, cesium (a blocker of If) should elim-
inate the positive chronotropic effect of NE. If Ica,L. is
involved,[Ca2+]0 should condition NE effects. We studied
the electrophysiological changes induced by NE in iso-
lated guinea pig SAN superfused in vitro with Tyrode
solution (both SAN dominant and subsidiary pacemaker
mechanisms are present) as well as with high [K+]o, high-
er Cs+ or Ba2+ (only the dominant pacemaker mechanism
is present). In Tyrode solution, NE (0.5-1uM) increased
the SAN rate and adding Cs+ (~12mM) caused a decay-
ing voltage tail during diastole in subsidiary pacemakers.
NE enhanced the Cs+-induced tail, and increased the rate
but less than in Tyrode solution. In higher [Cs+]o (15-
18mM), Ba2+ (1mM) or Ba2+ plus Cs+ (10mM) dominant
action potentials (not followed by a tail) were present
and NE accelerated them as in Tyrode solution. In high
[K+]o, NE increased the rate in the absence and presence
of Cs+, Ba2+ or Ba2+ plus Cs+. In these solutions, NE
increased the overshoot and maximum diastolic poten-
tial of dominant action potentials (Aps) and increased the
rate by steepening diastolic depolarization and shifting
the threshold for upstroke to more negative values. High
[Ca2+]o alone increased the rate and NE enhanced this
action, whereas low [Ca2+]o reduced or abolished the
increase in rate by NE. In SAN quiescent in high [K+]o
plus indapamide, NE induced spontaneous discharge by
decreasing the resting potential and initiating progres-
sively larger voltage oscillations.Thus, NE increases the
SAN rate by acting primarily on dominant Aps in a man-
ner consistent with an increase of Ica,L and Ik and under
conditions where If is either blocked or not activated. NE
initiates spontaneous discharge by inducing voltage os-
cillations unrelated to If. - 中文關鍵字: --
- 英文關鍵字: Sino-atrial node spontaneous discharge. Adrenergic control. Norepinephrine. Cesium. Barium. High indapamide. Hyperpolarization activated current. Slow inward current. Delayed rectifier current