IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Impact of mu-opioid receptor polymorphisms on neuronal calcium channels activity
Autor/es:
LÓPEZ SOTO, EDUARDO JAVIER; AGOSTI, FRANCINA; CATANESI CECILIA INÉS; RAINGO, JESICA
Lugar:
Huerta Grande, Cordoba
Reunión:
Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencia; 2011
Institución organizadora:
Sociedad Argentina de Investigacion en Neurociencia - SAN
Resumen:
The human mu-opioid receptor (hMOR) gene Single Nucleotide Polymorphism A118G/N40D (hMOR-D) has a high frequency of occurrence (~18%). Presence of hMOR-D in chronic pain patients is associated with lower morphine dose requirements. The molecular basis of this association is unknown. MOR activation inhibits presynaptic CaV2.2 calcium channels in nociceptors and, as a consequence, impairs synaptic transmission, reducing pain. Nociceptors are enriched in a CaV2.2 splicing isoform, named CaV2.2e37a, which has a distinct voltage independent sensitivity to MOR activation. Here, we hypothesized that hMOR-N or hMOR-D could differentially regulate CaV2.2e37a activity. To test this, we measured calcium currents in a heterologous system expressing either hMOR-N or hMOR-D and CaV2.2e37a. In dose-response curves for the MOR-agonist DAMGO, we found that hMOR-D has 4-fold higher potency and slightly higher efficiency to inhibit CaV2.2e37a currents, as compared to hMOR-N. Of note, the proportion of voltage dependent and voltage independent inhibition of CaV2.2e37a mediated by hMOR-N or hMOR-D was the same. Thus, we propose that the higher potency of hMOR-D on CaV2.2e37a contributes the lower morphine requirement in chronic pain patients.