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 nM) increased the L‐type Ca²⁺ 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 EC₅₀ value for increasing I_Ca was 5.2 nM. 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 μM) with an EC₅₀ value of 0.57 nM. Both the increase in I_Ca and the decrease in I_K.ACh were blocked by HOE140, a selective bradykinin B₂ 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 B₂‐receptor‐mediated I_K.ACh inhibition.