The primary structure of a voltage-dependent calcium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA. Calcium channel activity expressed from the cDNA is dramatically increased by coexpression of the alpha 2 and beta subunits, known to be associated with the dihydropyridine receptor. This channel is a high voltage-activated calcium channel that is insensitive both to nifedipine and to omega-conotoxin. We suggest that it is expressed predominantly in cerebellar Purkinje cells and granule cells.

Eur. J. Immunol. 17, 237 (1987

The complete amino acid sequence of the receptor for organic calcium channel blockers (CaCB) from rabbit lung has been deduced by cloning and sequence analysis of the cDNA. Synthetic RNA derived from this cDNA induces the formation of a functional CaCB-sensitive high voltage activated calcium channel in Xenopus oocytes.

Cyclic nucleotide-gated cation channels are essential in visual and olfactory signal transduction. An additional member of the cGMP-gated channel family, termed CNG-3, has been cloned from bovine kidney. Its deduced amino acid sequence is 60% and 62% identical with the CNG-channel proteins from bovine rod outer segment and bovine olfactory epithelium, respectively. Northern analysis and sequences amplified by the PCR showed that the CNG-3 mRNA is present in testis, kidney, and heart. Calcium permeated the expressed channel in the presence of extracellular Mg2+ and Na at membrane potentials from -100 to +45 mV.It is likely that CNG-3 protein is responsible for cGMP-induced Ca2+ entry in cells other than sensory cells.Cyclic GMP is a key regulatory molecule of specific cellular functions such as the visual transduction process (1, 2), relaxation of smooth muscle (3), intestinal secretion of water and salt (4), and reabsorption of Na+ and water in the distal tubule of the nephron (5). Overproduction of cGMP has been associated with neuronal degeneration, endotoxin shock, diarrhea, and loss of Na+ and water. These diverse cellular effects of cGMP are mediated by several distinct receptors: cGMP-stimulated and -inhibited phosphodiesterases (6), cGMP-dependent protein kinases (3), and cGMP-gated cation channels (1, 2). Cyclic nucleotide-gated (CNG) channels are essential in visual and olfactory signal transduction. These proteins [CNG-1 (7) and CNG-2 (8-10)] are encoded by two different genes. The CNG-1 channel is activated at 40-fold higher cGMP concentrations than the CNG-2 channel. An additional subunit confers high-affinity inhibition by L-cis-diltiazem to the rod photoreceptor channel (11). The native and expressed channels are nonspecific cation channels that are highly permeable to monovalent cations and are blocked by the divalent cations Mg2+ and Ca2+. In the presence of extracellular Mg2+ and Na+, Ca2+ permeates these channels at hyperpolarizing membrane potentials (see refs. 1, 2, and 12 for further discussion).So far, these channels seemed not to be expressed to a significant level in other tissues, although partial sequences of homologous channels have been amplified by PCR from kidney (13) and heart (14). A functional olfactory CNG-2-like channel has been cloned from a rabbit aorta library (10), but its tissue and cellular localization remained unsolved. However, a few reports suggested that cGMP-gated Ca2+ entry was mediated by CNG channels in nonsensory cells at depolarized membrane potentials (15-17). Apparently, a cGMP-gated channel mediated Ca2+ entry in calciumdepleted pancreatic acinar cells (15). Cultured renal epithelial A6 cells have a cGMP-stimulated cation-channel activity (16). Atrio-natriuretic factor, which stimulates cGMP production in the kidney, increased glomerular filtration by relaxation of preglomerular arterioles and contraction of postglomerular arterioles (17,18). This communication supports these reports and shows that bovine kidney expresses another member of the CNG-ch...

At least four calcium channel subtypes (P, T, N, and L) have now been classified on the basis of their biophysical and/or pharmacological properties. L-type channels, a channel family particularly important to physiological function of the cardiovascular system, are identified by their slow voltage- and calcium-dependent inactivation as well as their sensitivity to dihydropyridine (DHP) calcium channel antagonists. In this study, we report the results of experiments in which we have measured the DHP modulation of recombinant calcium channel activity in cells transfected with alpha 1 subunits of cardiac and smooth muscle L-type calcium channels. We find subunit-dependent differences in the voltage and concentration dependence of channel modulation. Our results provide evidence for a molecular basis for DHP sensitivity of heart and smooth muscle calcium channels and, additionally, indicate that, even within one family of calcium channels, slight differences in channel structure can cause marked differences in channel pharmacology.