Lower density of L-type and higher density of P/Q-type of calcium channels in chromaffin cells of hypertensive, compared with normotensive rats

Enhanced activity of the sympatho-adrenal axis and augmented circulating catecholamines has been implicated in the development of hypertension. Release of catecholamine from stimulated adrenal medulla chromaffin cells has been shown to be higher and longer in spontaneously hypertensive rats (SHRs), compared with normotensive Wistar rats (NWRs). Whether differences in the functional expression of voltage-dependent calcium channels (VDCCs) of the L-, N-, or P/Q subtypes may contribute to such distinct secretory behaviour, is unknown. We therefore approached here this study in voltage-clamped NWR and SHR chromaffin cells, using 10 mM Ba2+ as charge carrier (I-Ba) and selective blockers of each channel type. We found that compared with NWR cells, SHR chromaffin cells exhibited the following differences: (1) 30% diminution of the I-Ba fraction carried by L channels; (2) a doubling of the I-Ba fraction carried by P/Q channels; (3) more visible current modulation by ATP that could be linked to a 10-fold higher mRNA levels for purinergic receptors of the P-2Y2 subtype; and (3) a higher contribution of PQ channels to the transients of the cytosolic calcium concentrations ([Ca2+](c)) generated by K+, compared with L channels. These results may contribute to the better understanding of the greater calcium signalling and exocytotic responses of SHR compared with NWR chromaffin cells, found in three previous reports from our laboratories. (C) 2013 Elsevier B.V. All rights reserved.Government of SpainGovernment of BrazilCEAL-SANTANDER/UAMMinisterio de Economia y Competitividad, SpainRETICS, Instituto de Salud Carlos IIIMinisterio de Economia y CompetitividadUniv Autonoma Madrid, Fac Med, Inst Teofilo Hernando, E-28029 Madrid, SpainUniv Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, E-28029 Madrid, SpainUniv Autonoma Madrid, Serv Farmacol Clin, Inst Invest Sanitaria, Hosp Univ Princesa, E-28029 Madrid, SpainUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, São Paulo, BrazilUniv São Paulo, Inst Quim, Dept Bioquim, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, São Paulo, BrazilGovernment of Spain: PHB2011-0029-PCGovernment of Spain: PHB2011-0031-PCGovernment of Brazil: PHB2011-0029-PCGovernment of Brazil: PHB2011-0031-PCMinisterio de Economia y Competitividad, Spain: SAF2010-18837RETICS, Instituto de Salud Carlos III: RD 06/0026Ministerio de Economia y Competitividad: SAF2010-21795Web of Scienc