Characterization of effects of endothelin-1 on the L-type Ca2+ current in human atrial myocytes.
The effects of endothelin-1 (ET-1) on the L-type Ca2+ current (I(Ca)) were examined in whole cell patch-clamped human atrial myocytes. Depending on the initial current density, ET-1 (10 nM) increased the amplitude of I(Ca) by 99 +/- 7% or decreased it by 33 +/- 2%. The stimulatory effect predominated on current of low density (2.3 +/- 0.2 pA/pF), whereas I(Ca) of higher density (5.8 +/- 0.3 pA/pF) was inhibited by ET-1. After I(Ca) stimulation by 1 microM isoproterenol, ET-1 always inhibited the current by 32 +/- 7% (P < 0.05), an effect that was suppressed by pretreating myocytes with pertussis toxin. Atrial natriuretic peptide (ANP) inhibited I(Ca) (41 +/- 3%) by reducing intracellular cAMP concentration. In ANP-treated myocytes, the stimulatory effect of ET-1 on I(Ca) predominated (52 +/- 7%). The inhibitory effect of ET-1 on I(Ca) was blocked by the ET(A) antagonist BQ-123, whereas the stimulatory effect was suppressed by the ET(B) agonist BQ-788. We conclude that ET-1 has opposite effects on I(Ca) depending on the baseline amplitude of current, and both subtype ET receptors are implicated in the signal transduction pathways.
Boixel
C
C
Institut National de la Santé et de la Recherche Médicale U460, Faculté de Médecine Xavier Bichat, 75018 Paris, France.
Dinanian
S
S
Lang-Lazdunski
L
L
Mercadier
J J
JJ
Hatem
S N
SN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002648:Child; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques
D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D002118:Calcium