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The various splice variants of the three SERCA-and the two SPCA-pump genes in higher vertebrates encode P-type ATPases of the P 2A group found respectively in the membranes of the endoplasmic reticulum and the secretory pathway. Of these, SERCA2b and SPCA1a represent the housekeeping isoforms. The SERCA2b form is characterized by a luminal carboxy terminus imposing a higher affinity for cytosolic Ca 2þ compared to the other SERCAs. This is mediated by intramembrane and luminal interactions of this extension with the pump. Other known affinity modulators like phospholamban and sarcolipin decrease the affinity for Ca 2þ . The number of proteins reported to interact with SERCA is rapidly growing. Here, we limit the discussion to those for which the interaction site with the ATPase is specified: HAX-1, calumenin, histidine-rich Ca 2þ -binding protein, and indirectly calreticulin, calnexin, and ERp57. The role of the phylogenetically older and structurally simpler SPCAs as transporters of Ca 2þ , but also of Mn 2þ , is also addressed.

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A ~ S T R A C T A contraction of the rabbit ear artery can be induced by depolarizing the cells with a K-rich solution if Ca is present. 10 -9-10 -8 M noradrenaline and 10 -s-10 -7 M histamine cause a contraction of this tissue without modifying the membrane potential. If the histamine concentration exceeds 10 -~ M some depolarization of the membrane also occurs. Both noradrenaline and histamine also induce a contraction in Ca-free medium, even if La is present. None of these stimuli produces action potentials or fluctuations of the membrane potential. Besides these tonic contractions, the ear artery can also produce phasic contractions when 10 mM TEA is added to the medium. Such contractions are caused by the appearance of action potentials which are Ca dependent and which are similar to those appearing in visceral smooth muscle. A study of 4SCa fluxes has revealed that K depolarization and noradrenaline cause only a small increase in 4SCa uptake by the cells, while noradrenaline also releases cellular Ca, even in Ca-free medium. A comparison of tension development and 45Ca release induced by noradrenaline in Ca-free medium suggests that Ca extrusion could be very efficient in the rabbit ear artery and that it could play a direct role in its relaxation.

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We combined patch clamp and fura‐2 fluorescence methods to characterize human TRP3 (hTRP3) channels heterologously expressed in cultured bovine pulmonary artery endothelial (CPAE) cells, which do not express the bovine trp3 isoform (btrp3) but express btrp1 and btrp4. ATP, bradykinin and intracellular InsP3 activated a non‐selective cation current (IhTRP3) in htrp3‐transfected CPAE cells but not in non‐transfected wild‐type cells. During agonist stimulation, the sustained rise in [Ca2+]i was significantly higher in htrp3‐transfected cells than in control CPAE cells. The permeability for monovalent cations was PNa > PCs≈PK >> PNMDG and the ratio PCa/PNa was 1·62 ± 0·27 (n= 11). Removal of extracellular Ca2+ enhanced the amplitude of the agonist‐activated IhTRP3 as well as that of the basal current The trivalent cations La3+ and Gd3+ were potent blockers of IhTRP3 (the IC50 for La3+ was 24·4 ± 0·7 μM). The single‐channel conductance of the channels activated by ATP, assessed by noise analysis, was 23 pS. Thapsigargin and 2,5‐di‐tert‐butyl‐1,4‐benzohydroquinone (BHQ), inhibitors of the organellar Ca2+‐ATPase, failed to activate IhTRP3. U‐73122, a phospholipase C blocker, inhibited IhTRP3 that had been activated by ATP and bradykinin. Thimerosal, an InsP3 receptor‐sensitizing compound, enhanced IhTRP3, but calmidazolium, a calmodulin antagonist, did not affect IhTRP3. It is concluded that hTRP3 forms non‐selective plasmalemmal cation channels that function as a pathway for agonist‐induced Ca2+ influx.