The calcium antagonist D600 inhibits the calcium-independent transient outward current Ilo in rat ventricular and human atrial myocytes

1990 ◽  
Vol 22 ◽  
pp. S35
Author(s):  
I.A. Lefevre ◽  
B. Le Grand ◽  
A. Coulombe ◽  
E. Coraboeuf
Keyword(s):  
Calcium Antagonist ◽  
Outward Current ◽  
Transient Outward Current ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes

Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial myocytes

1995 ◽  
Vol 269 (2) ◽  
pp. H463-H472 ◽  
Author(s):  
G. R. Li ◽  
J. Feng ◽  
Z. Wang ◽  
B. Fermini ◽  
S. Nattel
Keyword(s):  
Outward Current ◽  
Pulse Frequency ◽  
Transient Outward Current ◽  
Tetraacetic Acid ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Atrial Cells ◽  
Whole Cell Patch Clamp ◽  
Current Voltage ◽  
Rabbit Atrium

The cardiac transient outward current (Ito) has been shown in several species to consist of two components: 1) a 4-aminopyridine (4-AP)-sensitive component (Ito1) and 2) a 4-AP-resistant component (Ito2). In rabbits, Ito2 is a Ca(2+)-dependent Cl- current [ICl(Ca)]; similar mechanisms have been suggested to underlie Ito2 in human atrium. We used whole cell patch-clamp techniques to define the mechanism of Ito2 (defined as the component resistant to 5 mM 4-AP) in human atrial myocytes, with parallel experiments performed in rabbit atrial cells. In rabbit atrium, Ito2 activated more slowly than Ito1 and had a bell-shaped current-voltage of Ito with properties similar to Ito2 in the rabbit, and a similar component recorded with pipette K+ replaced by Cs+ was suppressed by the substitution of methanesulfonate for Cl- in the superfusate. In human cells, a 4-AP-resistant Ito2 was recorded at a depolarizing pulse frequency of 1 Hz, but not at 0.1 Hz. Ito2 activated rapidly and inactivated earlier than Ito1, whereas its I-V relation was linear like that of Ito1. Ryanodine had no effect on human atrial Ito. When K(+)-free pipette solutions were used, no Ito was recorded in 30 human atrial myocytes, and external Cl- replacement with methanesulfonate failed to reveal an Ito. In 13 human myocytes, isoproterenol increased ICa but failed to activate an Ito compatible with ICl(Ca). Whereas caffeine suppressed human atrial Ito, it also suppressed Ito1 [in the presence of 200 microM Cd2+ to block ICa and 5 mM intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to buffer intracellular Ca2+] in both human and rabbit atrium, indicating an action unrelated to Ca(2+)-triggered Ca2+ release. In conclusion, we were unable to demonstrate the presence of ICl(Ca) in human atrial myocytes, and the 4-AP-resistant component of Ito appeared to be due to 4-AP unblocking.

Role of chloride currents in repolarizing rabbit atrial myocytes

1995 ◽  
Vol 268 (5) ◽  
pp. H1992-H2002 ◽  
Author(s):  
Z. Wang ◽  
B. Fermini ◽  
J. Feng ◽  
S. Nattel
Keyword(s):  
Action Potential ◽  
Reversal Potential ◽  
Outward Current ◽  
Cell Voltage ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Atrial Myocytes ◽  
Atrial Cells ◽  
K Current

Rabbit atrial cells manifest a prominent transient outward K+ current (Ito1), but this current recovers slowly from inactivation and is unlikely to be important at physiological rates (3-5 Hz). Depolarization of rabbit atrial cells also elicits a transient Ca(2+)-dependent outward Cl- current (Ito2). To compare the relative magnitude of these transient outward currents at various rates, we applied whole cell voltage-clamp techniques to isolated rabbit atrial myocytes. Whereas peak Ito1 exceeded Ito2 at slow rates (0.1 Hz), Ito1 was strongly reduced as rate was increased (by 97 +/- 2%, mean +/- SE, at 4 Hz), while Ito2 was slightly reduced (by 28 +/- 4%, 4 Hz). The reversal potential of transient outward tail currents at 0.07 Hz was -49 +/- 9 mV, while at 2.5 Hz the reversal potential became -18 +/- 7 mV (calculated Cl- reversal potential -18 mV). The addition of the Cl- transport blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 150 microM) or the replacement of external Cl- with methanesulfonate inhibited a large part of the transient outward current elicited by depolarization at 4 Hz. DIDS and Cl- replacement increased action potential duration in both single rabbit atrial cells and multicellular rabbit atrial preparations. We conclude that the Ca(2+)-dependent Cl- current is substantially larger than the transient K+ current at physiological rates in the rabbit and is likely to play a more important role in action potential repolarization than the latter current in this tissue in vivo.

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