Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the α1D Ca2+ channel

Segura-Chama P, Rivera-Cerecedo CV, Gonzalez-Ramirez R, Felix R, Hernandez-Guijo JM, Hernandez-Cruz A. Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the alpha(1D) Ca2+ channel. Am J Physiol Heart Circ Physiol 302: H467-H478, 2012. First published November 11, 2011; doi: 10.1152/ajpheart.00849.2011.-Ca2+ currents (I-Ca) recorded from adrenal chromaffin cells (CCs) of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats are similar to one another, but different from those recorded in other rodent species. I-Ca in WKY/SHR CCs comprises an early, transient (I-Cae) and a late, sustained component (I-Cas). In Wistar CCs, I-Cae is absent, and I-Cas is of greater amplitude. Activation and steady-state inactivation of I-Cae and I-Cas in WKY/SHR CCs suggest the recruitment of at least two populations of Ca2+ channels with different voltage dependence and kinetics. In WKY/SHR CCs, I-Cae is inhibited by nifedipine, enhanced by BAY K 8644, is not blocked by the mibefradil analog NNC 55-0396, and displays Ca2+-dependent inactivation and fast deactivation kinetics, suggesting that it results from the opening of L-type rather than T-type Ca2+ channels. I-Cae properties suggest that it originates from the opening of Ca2+ channels formed with the short splice variant (Ca(V)1.3(42A)). RTPCR showed that expression of Ca(V)1.3(42A) mRNA is similar in both Wistar and WKY/SHR, but that the long variant (Ca(V)1.3(42)) is virtually absent in WKY/SHR. Thus I-Cae corresponds to the recruitment of Ca(V)1.3(42A) channels, unmasked by the absence of Ca(V)1.3(42) channels. Studies in WKY CCs do not report major functional alterations, despite the unusual expression pattern of Ca(V)1.3 splice variants. It remains to be established if more subtle functional alterations exist, and if the atypical splicing pattern of Ca(V)1.3 could be related to the functional and behavioral alterations reported in WKY/SHR rats, including their susceptibility to develop hypertension.