Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
Background and purpose: Na⁺/HCO<sub>3</sub>⁻ co-transport (NBC) regulates intracellular pH (pH<sub>i</sub>) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. Experimental approach: We generated...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2011
|
| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/97962 https://ri.conicet.gov.ar/11336/61760 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2011.01496.x |
| Aporte de: |
| id |
I19-R120-10915-97962 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Medicina Cardiac myocytes Functional antibodies Na⁺/HCO3⁻ co-transporter |
| spellingShingle |
Medicina Cardiac myocytes Functional antibodies Na⁺/HCO3⁻ co-transporter De Giusti, Verónica Celeste Orlowski, Alejandro Villa Abrille, María Celeste Chiappe de Cingolani, Gladys Ethel Casey, Joseph R. Álvarez, Bernardo Víctor Aiello, Ernesto Alejandro Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| topic_facet |
Medicina Cardiac myocytes Functional antibodies Na⁺/HCO3⁻ co-transporter |
| description |
Background and purpose: Na⁺/HCO<sub>3</sub>⁻ co-transport (NBC) regulates intracellular pH (pH<sub>i</sub>) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein.
Experimental approach: We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pH<sub>i</sub> was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H⁺ flux, J<sub>H</sub>, in mmol·L<sup>-1</sup> min<sup>-1</sup> at pH<sub>i</sub> 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpH<sub>i</sub>) respectively.
Key results: The potassium pulse produced a pH<sub>i</sub> increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased J<sub>H</sub> by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pH<sub>i</sub> increase than control,(0.25 ± 0.018) whereas the recovery of pH<sub>i</sub> from acidosis was faster (J<sub>H</sub> was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively.
Conclusions and implications: Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. |
| format |
Articulo Articulo |
| author |
De Giusti, Verónica Celeste Orlowski, Alejandro Villa Abrille, María Celeste Chiappe de Cingolani, Gladys Ethel Casey, Joseph R. Álvarez, Bernardo Víctor Aiello, Ernesto Alejandro |
| author_facet |
De Giusti, Verónica Celeste Orlowski, Alejandro Villa Abrille, María Celeste Chiappe de Cingolani, Gladys Ethel Casey, Joseph R. Álvarez, Bernardo Víctor Aiello, Ernesto Alejandro |
| author_sort |
De Giusti, Verónica Celeste |
| title |
Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| title_short |
Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| title_full |
Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| title_fullStr |
Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| title_full_unstemmed |
Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools |
| title_sort |
antibodies against the cardiac sodium/bicarbonate co-transporter (nbce1) as pharmacological tools |
| publishDate |
2011 |
| url |
http://sedici.unlp.edu.ar/handle/10915/97962 https://ri.conicet.gov.ar/11336/61760 https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2011.01496.x |
| work_keys_str_mv |
AT degiustiveronicaceleste antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT orlowskialejandro antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT villaabrillemariaceleste antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT chiappedecingolanigladysethel antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT caseyjosephr antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT alvarezbernardovictor antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools AT aielloernestoalejandro antibodiesagainstthecardiacsodiumbicarbonatecotransporternbce1aspharmacologicaltools |
| bdutipo_str |
Repositorios |
| _version_ |
1764820492509773827 |