title: Oxygen tension modulates inhibition of L-type calcium currents by isoflurane in human atrial cardiomyocytes.
abstract: BACKGROUND
  Myocardial L-type Ca(2+) currents (I(Ca,L)) are inhibited by isoflurane in the presence of a partial pressure of oxygen (P(O2)) of 150 mmHg. In guinea pig cardiomyocytes, I(Ca,L) are inhibited by reduced oxygen tensions. The authors therefore analyzed the effects of P(O2) on I(Ca,L) in human cardiomyocytes and the effects of isoflurane at reduced P(O2).
  
  
  METHODS
  Atrial cardiomyocytes were prepared from specimens of patients undergoing open-heart surgery and superfused with either a high or a low P(O2) (150 or 12 +/- 1 mmHg) while I(Ca,L) were measured with the whole cell patch clamp technique.
  
  
  RESULTS
  Basal I(Ca,L) were not changed by the P(O2) (range, 9-150 mmHg) at 21 degrees or 36 degrees C. The reducing agent 1,4-dithiothreitol (DTT) left I(Ca,L) unaffected, and the oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) irreversibly inhibited I(Ca,L). The P(O2) significantly affected the inhibition of I(Ca,L) by isoflurane (1 minimum alveolar concentration) that decreased I(Ca,L) by 17 +/- 2.0% at the high P(O2) but only by 5.8 +/- 2.9% (P = 0.037) at the low P(O2). The inhibition of I(Ca,L) by isoflurane was also significantly diminished (P = 0.018) by a low P(O2) when isoflurane effects at both P(O2) conditions were compared in the same cell.
  
  
  CONCLUSIONS
  In contrast to the situation in guinea pigs, basal I(Ca,L) in human atrial cardiomyocytes was not sensitive to acute P(O2) changes over a wide range. This might be explained by a lack of oxygen-sensitive splice variants of L-type calcium channel subunits. The P(O2), however, has a decisive role for the effects of isoflurane on I(Ca,L).
authors.affiliation: Institute of Physiology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Kowark
authors.forename: Rocco
authors.initials: R
authors.lastname: Hüneke
authors.forename: Eberhard
authors.initials: E
authors.lastname: Jüngling
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Andreas
authors.initials: A
authors.lastname: Lückhoff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006325:Heart Atria; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D020746:Calcium Channels, L-Type; D007530:Isoflurane; D010100:Oxygen; D004229:Dithiothreitol