Atypical caspi 2+ currents in chromaffin cells from shr and wky rat strains result from the deficient expression of a splice variant of the α1D caspi 2+channel

摘要

Ca 2+ currents (ICa) 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. ICa in WKY/SHR CCs comprises an early, transient (ICa e) and a late, sustained component (ICas). In Wistar CCs, ICa e is absent, and ICa s is of greater amplitude. Activation and steady-state inactivation of ICae and ICas in WKY/SHR CC s suggest the recruitment of at least two populations of Ca 2+ channels with different voltage dependence and kinetics. In WKY/SHR CCs, Ica e is inhibited by nifedipine, enhanced by BAY K 8644, is not blocked by the mibefradil analog NNC 55-0396, and displays Ca 2+-dependent inactivation and fast deactivation kinetics, suggesting that it results from the opening of L-type rather than T-type Ca 2+ channels. ICae properties suggest that it originates from the opening of Ca 2+ channels formed with the short splice variant (CaV1.342A). RTPCR showed that expression of Ca V1.3 42A mRNA is similar in both Wistar and WKY/SHR, but that the long variant (CaV1.342) is virtually absent in WKY/SHR. Thus ICae corresponds to the recruitment of CaV1.3 42A channels, unmasked by the absence of Ca V1.3 42 channels. Studies in WKY CCs do not report major functional alterations, despite the unusual expression pattern of Ca V1.3 splice variants. It remains to be established if more subtle functional alterations exist, and if the atypical splicing pattern of Ca V1.3 could be related to the functional and behavioral alterations reported in WKY/SHR rats, including their susceptibility to develop hypertension.