Ca-antagonistic effects of adenosine in guinea pig atrial cells

In atrial myocytes of the guinea pig, the effects of adenosine (Ado) and acetylcholine (ACh) on Ca currents (ICa) were investigated with the patch-electrode whole cell clamp technique. ICa was dissected from net currents by blocking K currents (IK) with intra- and extracellular Cs ions. ICa was considered as "basal" ICa, since it was not prestimulated by beta-agonists (isoproterenol). T-channel Ca currents were insensitive to Ado or ACh. The antagonism of L-channel Ca currents was maximal with 10 microM Ado or 3 microM ACh, which reduced basal ICa by 35%. From the concentration dependence, a dissociation constant (KD) value of 1.1 microM Ado and a Hill coefficient of -3 were obtained. Ado and ACh were not additive but saturative in reducing basal ICa. Reduction of basal ICa did not modify inactivation time-course, steady-state activation or inactivation, suggesting that Ado reduces the number of functional Ca channels. In myocytes with unblocked IK (KCl electrodes), 3 microM Ado (1 microM ACh) reduced ICa by 30% but increased IK by 300%. It is concluded that the K-agonistic rather than the Ca-antagonistic effect accounts for hyperpolarization as well as for most of the shortening of the action potential and the negative inotropy.