| Background Chloride channels participate in a wide variety of cell and intracellular organelle functions, including regulation of electrical activity, transepithelial transport, cell volume regulation, acidification of intracellular organelles, and may even play a role in the control of immunological responses, cell migration, cell proliferation and differentiation. These different functions require the presence of many distinct chloride channels coded by different genes. Voltage-gated chloride channels(C1C) is one family of chloride channels, and C1C genes are present in organisms as diverse as animals, plants, yeasts and bacteria. So far nine members of this family have been found and cloned from mammals. The loss or defection of functions resulting from mutations in these channels results in several human inherited diseases, such as myotonia congenita, kidney stones, Bartter抯 syndrome. dC-I chloride 11 channel(C IC- 1) is the first cloned member in mammals which is predominantly expressed in skeletal muscle and also can be detected in heart, kidney and smooth muscle. The current studies show that C1C-l is tightly linked with myotonia congenita. CIC-l was specially emphasized over the past decade because of its first position in mammal C1C channels. Almost all studies of C1C- I concentrated on the relationships among the structure, function and disease because C1C-l was cloned from skeletal muscle and is in fact the direct cause of myotonia due to the loss of function or decrease of channel conductance. So far a variety of results have been obtained. However, many important questions in this field are still not clear, including the correlation between the structure and function, the voltage gating mechanism and blocking property of the channel. Especially, there has no any report of C1C- I splicing isoforms, also no further work to check the tissue distribution and expression of C1C- I except skeletal muscle since Steinmeyer抯 report in 1991, which make it impossible for us to understand the complexity of structures and diversity of the functions of dC-i. Because of the ubiquitous distributions, similarities of complementary DNA (cDNA) and amino acid sequences in different C1C members, and the cloned splicing isoforms of C1C-2, C1C-3, C1C-6 and C1C-K2, it is reasonable to predict that there should be splicing isoforms of did-i, and also C1C-1 can probably be expressed in nonexcitable tissues or other excitable tissues except skeletal muscle. Chloride channels play very important roles in regulation of C6 glioma cell functions, and there exists an interaction between the astrocyte 12 chloride channels and receptor chloride channels of neuron cells, thus, further study of C6 chloride channels is needed. However, it is not clear what kind of chloride channels are expressed in C6 cells except volume- sensitive chloride channel. Therefore, it is necessary to check the expression and to study the function of C1C channles in C6 cells. Besides, it was reported that several C1C members including C1C-l are expressed in heart, so the study of C1C- 1 will help us to understand the functions of C1C channels in heart. Specific Aims The goal of this paper is to study the dC-i channel at gene and function levels by ef...
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