Adenosine-induced changes in atrial action potential: Contribution of Ca and K currents

In this study, we examined the relative contribution of the increase in acetylcholine-regulated potassium current (I(K ACh)) and decrease in calcium current (I(Ca)) to the adenosine (Ado)-induced shortening of action potential duration (APD). In isolated guinea pig atrial myocytes, membrane potentials and currents were measured by the whole cell patch-clamp technique. I(Ca) and I(K ACh) were individualized by blocking the K currents with Cs⁺ and I(Ca) with Cd²⁺. The effects of Ado on membrane potential and currents were concentration dependent. Ado (10 μM) shortened APD at 0 mV and at 90% of repolarization (APD_{0, 90}) to 7 ± 1 and 26 ± 6 ms from control values of 23 ± 3 and 89 ± 6 ms, respectively. Concomitant with the changes in APD, Ado decreased I(Ca) from -9.2 ± 1.3 to -6.8 ± 10 μA/μF (26% decrease) but increased I(K ACh) from +3.5 ± 0.5 to +7.8 ± 0.8 μA/μF (123% increase). When rundown of I(Ca) was taken into account, the maximum decrease in I(Ca) caused by Ado was 12%. The effect of Ado on I(Ca) and I(K ACh) was not altered by treatment of the cells with either Cs⁺ or Cd²⁺. The shortening of APD_{0, 90} strongly correlated with the increase in I(K ACh) but minimally with the decrease in I(Ca). A 22% reduction in I(Ca) caused by lowering extracellular Ca²⁺ concentration ([Ca²⁺](o)) from 3.6 to 1.8 mM was associated with an 11 and 14% shortening of APD₀ and APD₉₀, respectively. In the same myocytes an 18% decrease in I(Ca) by 10 μM Ado reduced APD₀ and APD₉₀ by 58 and 61%, respectively. In conclusion, the effects of Ado on membrane potential in atrial myocytes are predominantly due to activation of I(K ACh).