Y. Habuchi et al., ANGIOTENSIN-II INHIBITION OF L-TYPE CA2+ CURRENT IN SINOATRIAL NODE CELLS OF RABBITS, American journal of physiology. Heart and circulatory physiology, 37(3), 1995, pp. 1053-1060
The actions of angiotensin II (ANG II) were examined in the spontaneou
sly active cells isolated from the rabbit sinoatrial node, using the n
ystatin-permeabilized, whole cell, patch-clamp method. At 30 nM, ANG I
I significantly lowered the spontaneous firing rate of the action pote
ntials from 212 +/- 21 to 172 +/- 32 beats/min, with a concomitant red
uction in the action potential amplitude. The voltage-clamp experiment
s showed that ANG II inhibited the L-type Ca2+ current (I-Ca) with a d
issociation constant (K-d) of similar to 4 nM and a maximal inhibition
of 30%. The inhibition was blocked by an AT(1)-receptor antagonist CV
11974. Acetylcholine (ACh) at 10 mu M reduced the I-Ca by 42 +/- 12%,
and ANG II did not cause any further inhibition in the presence of ACh
. At 100 nM, ANG II reduced the I-Ca by only 12% in the presence of 2
mu M isoproterenol, and a similar inhibition was observed with 0.1 mu
M ACh. ANG II did not affect the dibutyryl adenosine 3',5'-cyclic mono
phosphate-stimulated I-Ca. Protein kinase C activator 12-O-tetra-decan
oylphorbol-13-acetate did not mimic ANG II in the effects on I-Ca, and
preincubation of the cells with calphostin C, a protein kinase C inhi
bitor, did not attenuate the ANG II effect. ANG II exerts a negative c
hronotropic effect in the pacemaker cells as its direct action through
a pathway involving adenosine 3',5'-cyclic monophosphate-dependent pr
otein kinase.