The Na(+)/Ca(2+)exchanger (NCX) principal function is taking 1 Ca(2+) out of the cytoplasm and introducing 3 Na(+). The increase of cytoplasmic Na(+) concentration induces the NCX reverse mode (NCX(REV)), favoring Ca(2+) influx. NCX(REV) can be inhibited by: KB-R7943 a non-specific compound that blocks voltage-dependent and store-operated Ca(2+) channels; SEA0400 that appears to be selective for NCX(REV), but difficult to obtain and SN-6, which efficacy has been shown only in cardiomyocytes. We found that PPADS, a P2X receptor antagonist, acts as a NCX(REV) inhibitor in guinea pig tracheal myocytes. In these cells, we characterized the NCX(REV) by substituting NaCl and NaHCO(3) with LiCl, resulting in the increase of the intracellular Ca(2+) concentration ([Ca(2+)]i) using fura 2-AM. We analyzed 5 consecutive responses of the NCX(REV) every 10 min, finding no differences among them. To evaluate the effect of different NCX(REV) blockers, concentration response curves to KB-R7943 (1, 3.2 and 10 μM), and SN-6 (3.2, 10 and 30 μM) were constructed, whereas PPADS effect was characterized as time- and concentration-dependent (1, 3.2, 10 and 30 μM). PPADS had similar potency and efficacy as KB-R7943, whereas SN-6 was the least effective. Furthermore, KCl-induced contraction, sensitive to D600 and nifedipine, was blocked by KB-R7943, but not by PPADS. KCl-induced [Ca(2+)]i increment in myocytes was also significantly decreased by KBR-7943 (10 μM). Our results demonstrate that PPADS can be used as a reliable pharmacological tool to inhibit NCX(REV), with the advantage that it is more specific than KB-R7943 because it does not affect L-type Ca(2+) channels.
The Na(+)/Ca(2+)exchanger ( NCX ) principal function is taking 1 Ca(2 + ) out of the cytoplasm and introducing 3 Na(+ ) . The increase of cytoplasmic Na(+ ) concentration induces the NCX reverse mode ( NCX(REV ) ) , favoring Ca(2 + ) influx . NCX(REV ) can be inhibited by : KB - R7943 a non - specific compound that blocks voltage - dependent and store - operated Ca(2 + ) channels ; SEA0400 that appears to be selective for NCX(REV ) , but difficult to obtain and SN-6 , which efficacy has been shown only in cardiomyocytes . We found that PPADS , a P2X receptor antagonist , acts as a NCX(REV ) inhibitor in guinea pig tracheal myocytes . In these cells , we characterized the NCX(REV ) by substituting NaCl and NaHCO(3 ) with LiCl , resulting in the increase of the intracellular Ca(2 + ) concentration ( [ Ca(2+)]i ) using fura 2-AM . We analyzed 5 consecutive responses of the NCX(REV ) every 10 min , finding no differences among them . To evaluate the effect of different NCX(REV ) blockers , concentration response curves to KB - R7943 ( 1 , 3.2 and 10 μM ) , and SN-6 ( 3.2 , 10 and 30 μM ) were constructed , whereas PPADS effect was characterized as time- and concentration - dependent ( 1 , 3.2 , 10 and 30 μM ) . PPADS had similar potency and efficacy as KB - R7943 , whereas SN-6 was the least effective . Furthermore , KCl - induced contraction , sensitive to D600 and nifedipine , was blocked by KB - R7943 , but not by PPADS . KCl - induced [ Ca(2+)]i increment in myocytes was also significantly decreased by KBR-7943 ( 10 μM ) . Our results demonstrate that PPADS can be used as a reliable pharmacological tool to inhibit NCX(REV ) , with the advantage that it is more specific than KB - R7943 because it does not affect L - type Ca(2 + ) channels .
The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?
The small molecule SEA0400 is an inhibitor of which ion antiporter / exchanger ?
NCX
Na(+)/Ca(2+) exchanger NCX