The purpose of this study was to investigate the effects of calcitonin gene-related peptide (CGRP) on the repolarization process in isolated guinea-pig atrial cells and to determine the contribution of K(+) channels to the CGRP-induced changes in action potential using conventional microelectrode method at the physiological temperature. We found that: (1) CGRP (16 nmol/L) antagonized the influences of potassium channel blockers, 4-AP and BaCl2, on action potential; (2) CGRP (16 nmol/L) increased the amplitude and maximum depolarizing velocity of slow action potential and shortened the conducting time in guinea pig atrial myocardium at extracellular K(+) concentration of 18.5 mmol/L; (3) CGRP (16 nmol/L) alleviated triggered activity induced by superfusion with solution containing CsCl and no potassium ion; and (4) the effects of CGRP on the configuration of action potential were temperature-dependent. At the temperature of 36.5+/-0.5 degrees C, CGRP (5, 16, and 50 nmol/L) increased the amplitude of the action potential and shortened APD(20), APD(50) and APD(90). The CGRP effects on APD(20) and APD(50) were dose-dependent and reversible. On the contrary, CGRP prolonged APD(20), APD(50) and APD(90) at the temperature of 25.5+/-2.1 degrees C. The present study suggests that CGRP possesses multiple effects on various ionic channels. Among them the effects on potassium currents are major determinants in the changes in action potential induced by CGRP under physiological temperature. It is necessary to further study the influences of CGRP on different types of potassium channels.