Oxygen tension modulates inhibition of L-type calcium currents by isoflurane in human atrial cardiomyocytes

Pascal Kowark, Rocco Hüneke, Eberhard Jüngling, Rolf Rossaint, Andreas Lückhoff

Research output: Contribution to journalArticlepeer-review

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BACKGROUND: Myocardial L-type Ca 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° or 36°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. CONCLUSIONS: In contrast to the situation in guinea pigs, basal ICa,L in human atrial cardiomyocytes was not sensitive to acute Po2 changes over a wide range. This might be explained by a lack of oxygen-sensitive splice variants of L-type calcium channel subunits. The Po2, however, has a decisive role for the effects of isoflurane on ICa,L.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
Issue number4
StatePublished - Apr 2007


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