The reverse mode of the Na+/Ca2+ exchanger contributes to the pacemaker mechanism in rabbit sinus node cells
Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca 2+ -handling. The fundamental role of the inward Na + /Ca 2+ exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed imp...
Elmentve itt :
| Szerzők: | |
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2022
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| Sorozat: | SCIENTIFIC REPORTS
12 |
| Tárgyszavak: | |
| doi: | 10.1038/s41598-022-25574-8 |
| mtmt: | 33364863 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/25845 |
| LEADER | 02484nab a2200313 i 4500 | ||
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| 005 | 20221219150510.0 | ||
| 008 | 221219s2022 hu o 0|| Angol d | ||
| 022 | |a 2045-2322 | ||
| 024 | 7 | |a 10.1038/s41598-022-25574-8 |2 doi | |
| 024 | 7 | |a 33364863 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Tóth Noémi | |
| 245 | 1 | 4 | |a The reverse mode of the Na+/Ca2+ exchanger contributes to the pacemaker mechanism in rabbit sinus node cells |h [elektronikus dokumentum] / |c Tóth Noémi |
| 260 | |c 2022 | ||
| 300 | |a 16 | ||
| 490 | 0 | |a SCIENTIFIC REPORTS |v 12 | |
| 520 | 3 | |a Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca 2+ -handling. The fundamental role of the inward Na + /Ca 2+ exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed important role to reverse NCX activity, however experimental evidence is still missing. Whole-cell and perforated patch-clamp experiments were performed on rabbit SN cells supplemented with fluorescent Ca 2+ -tracking. We established 2 and 8 mM pipette NaCl groups to suppress and enable reverse NCX. NCX was assessed by specific block with 1 μM ORM-10962. Mechanistic simulations were performed by Maltsev–Lakatta minimal computational SN model. Active reverse NCX resulted in larger Ca 2+ -transient amplitude with larger SR Ca 2+ -content. Spontaneous action potential (AP) frequency increased with 8 mM NaCl. When reverse NCX was facilitated by 1 μM strophantin the Ca 2+ i and spontaneous rate increased. ORM-10962 applied prior to strophantin prevented Ca 2+ i and AP cycle change. Computational simulations indicated gradually increasing reverse NCX current, Ca 2+ i and heart rate with increasing Na + i . Our results provide further evidence for the role of reverse NCX in SN pacemaking. The reverse NCX activity may provide additional Ca 2+ -influx that could increase SR Ca 2+ -content, which consequently leads to enhanced pacemaking activity. | |
| 650 | 4 | |a Általános orvostudomány | |
| 700 | 0 | 1 | |a Loewe Axel |e aut |
| 700 | 0 | 1 | |a Szlovák Jozefina |e aut |
| 700 | 0 | 1 | |a Kohajda Zsófia |e aut |
| 700 | 0 | 1 | |a Bitay Gergő |e aut |
| 700 | 0 | 1 | |a Levijoki Jouko |e aut |
| 700 | 0 | 1 | |a Papp Gyula |e aut |
| 700 | 0 | 1 | |a Varró András |e aut |
| 700 | 0 | 1 | |a Nagy Norbert |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/25845/1/Toth_et_al_SREP.pdf |z Dokumentum-elérés |