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 :
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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 |
| Tartalmi kivonat: | 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. |
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| Terjedelem/Fizikai jellemzők: | 16 |
| ISSN: | 2045-2322 |