Correlation of Sinus Slowing and Hyperpolarization Caused by Adenosine in Sinus Node

The effect of adenosine on sinus node cells was examined in a preparation that precluded pacemaker shift. It was found that adenosine produced a dose-dependent slowing in rate. In examining the effects on the action potential parameters (n = 10), adenosine caused a significant increase in the maximum diastolic potential (control = -62 +/- 2 mV, adenosine, 1 X 10(-4) M, = -67 +/- 3 mV) and a significant increase in the rate of rise of the action potential (control = 3.3 +/- 0.6 V/s, adenosine, 1 X 10(-4) M, = 7.2 +/- 2 V/s). There was only a slight shortening of the action potential duration and a small increase in the action potential overshoot. Adenosine caused a significant decrease in the rate of diastolic depolarization (control = 100 +/- 19 mV/s, adenosine, 1 X 10(-4) M, = 42 +/- 5 mV/s). Acetylcholine caused similar effects. The effects of adenosine were not affected by atropine or propranolol but were antagonized by aminophylline, an adenosine competitive antagonist. In another set of experiments (n = 12) we sought to understand further the mechanism of sinus slowing caused by adenosine and compare with the effects of acetylcholine. The increase in cycle length due to different doses of adenosine and acetylcholine was measured. The preparation was then arrested with D-600 or NiCl2. The cells were then exposed to the same concentrations of adenosine and acetylcholine and the amount of hyperpolarization from the resting potential (means = -40 +/- 4 mV) was measured. The change in cycle length and amount of hyperpolarization were linearly correlated (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)