Oxygen Tension Modulates Inhibition of L-type Calcium Currents by Isoflurane in Human Atrial Cardiomyocytes

Background: Myocardial L-type Ca2+ currents (ICa,L) are inhibited by isoflurane in the presence of a partial pressure of oxygen (Po2) of 150 mmHg. In guinea pig cardiomyocytes, ICa,L are inhibited by reduced oxygen tensions. The authors therefore analyzed the effects of Po2 on ICa,L in human cardiomyocytes and the effects of isoflurane at reduced Po2.

Methods: Atrial cardiomyocytes were prepared from specimens of patients undergoing open-heart surgery and superfused with either a high or a low Po2 (150 or 12 +/- 1 mmHg) while ICa,L were measured with the whole cell patch clamp technique.

Results: Basal ICa,L were not changed by the Po2 (range, 9-150 mmHg) at 21[degrees] or 36[degrees]C. The reducing agent 1,4-dithiothreitol (DTT) left ICa,L unaffected, and the oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) irreversibly inhibited ICa,L. The Po2 significantly affected the inhibition of ICa,L by isoflurane (1 minimum alveolar concentration) that decreased ICa,L by 17 +/- 2.0% at the high Po2 but only by 5.8 +/- 2.9% (P = 0.037) at the low Po2. The inhibition of ICa,L by isoflurane was also significantly diminished (P = 0.018) by a low Po2 when isoflurane effects at both Po2 conditions were compared in the same cell.