Bradykinin B 2 ‐receptor‐mediated modulation of membrane currents in guinea‐pig cardiomyocytes
In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)‐induced positive inotropic and chronotropic responses in isolated guinea‐pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques. BK (0.1–1000 n M )...
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| Published in | British journal of pharmacology Vol. 125; no. 2; pp. 283 - 292 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
03.02.2009
|
| Online Access | Get full text |
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| Summary: | In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)‐induced positive inotropic and chronotropic responses in isolated guinea‐pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques.
BK (0.1–1000 n
M
) increased the L‐type Ca
2+
current (I
Ca
), which was recorded from enzymatically‐dissociated atrial myocytes by the nystatin‐perforated patch method, in a concentration‐dependent fashion, and the calculated EC
50
value for increasing I
Ca
was 5.2 n
M
. In conventional ruptured patch experiments, BK inhibited the muscarinic acetylcholine receptor‐operated K
+
current (I
K.ACh
) that was activated by the muscarinic agonist carbachol (1 μ
M
) with an EC
50
value of 0.57 n
M
. Both the increase in I
Ca
and the decrease in I
K.ACh
were blocked by HOE140, a selective bradykinin B
2
receptor antagonist.
The BK‐induced inhibition of I
K.ACh
was significantly attenuated by staurosporine and calphostin C, protein kinase C inhibitors. In addition, the I
K.ACh
inhibition by BK was also attenuated by the tyrosine kinase inhibitor genistein or tyrphostin but not by daidzein, an inactive analogue of genistein. However, neither protein kinase C inhibitor nor tyrosine kinase inhibitor affected the BK‐induced increase in I
Ca
.
In the presence and absence of muscarinic stimulation, BK prolonged the action potential recorded from the atrial cells in the current clamp mode.
We conclude that BK increases I
Ca
and decreases I
K.ACh
in atrial cells, resulting in positive inotropic and chronotropic responses in atrial preparations. Protein kinase C activation, and possibly tyrosine kinase activation, may be involved in the B
2
‐receptor‐mediated I
K.ACh
inhibition.
British Journal of Pharmacology
(1998)
125
, 283–292; doi:
10.1038/sj.bjp.0702060 |
|---|---|
| ISSN: | 0007-1188 1476-5381 |
| DOI: | 10.1038/sj.bjp.0702060 |