Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel.
Skeletal muscle is unusual in that 70-85% of resting membrane conductance is carried by chloride ions. This conductance is essential for membrane-potential stability, as its block by 9-anthracene-carboxylic acid and other drugs causes myotonia. Fish electric organs are developmentally derived from skeletal muscle, suggesting that mammalian muscle may express a homologue of the Torpedo mamorata electroplax chloride channel. We have now cloned the complementary DNA encoding a rat skeletal muscle chloride channel by homology screening to the Cl- channel from Torpedo. It encodes a 994-amino-acid protein which is about 54% identical to the Torpedo channel and is predominantly expressed in skeletal muscle. Messenger RNA amounts in that tissue increase steeply in the first 3-4 weeks after birth, in parallel with the increase in muscle Cl- conductance. Expression from cRNA in Xenopus oocytes leads to 9-anthracene-carboxylic acid-sensitive currents with time and voltage dependence typical for macroscopic muscle Cl- conductance. This and the functional destruction of this channel in mouse myotonia suggests that we have cloned the major skeletal muscle chloride channel.
Steinmeyer
K
K
Centre for Molecular Neurobiology (ZMNH), Hamburg University, Germany.
Ortland
C
C
Jentsch
T J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D003001:Cloning, Molecular; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D024510:Muscle Development; D009132:Muscles / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D014982:Xenopus laevis
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D012333:RNA, Messenger