Oxygen tension modulates inhibition of L-type calcium currents by isoflurane in human atrial cardiomyocytes.
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).
Kowark
Pascal
P
Institute of Physiology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
Hüneke
Rocco
R
Jüngling
Eberhard
E
Rossaint
Rolf
R
Lückhoff
Andreas
A
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*
D018685:Anesthetics, Inhalation; D020746:Calcium Channels, L-Type; D007530:Isoflurane; D010100:Oxygen; D004229:Dithiothreitol