Es. Piedrasrenteria et al., ANTISENSE OLIGONUCLEOTIDES AGAINST RAT-BRAIN ALPHA(1E) DNA AND ITS ATRIAL HOMOLOG DECREASE T-TYPE CALCIUM CURRENT IN ATRIAL MYOCYTES, Proceedings of the National Academy of Sciences of the United Statesof America, 94(26), 1997, pp. 14936-14941
Low voltage-activated, or T-type, calcium currents are important regul
ators of neuronal and muscle excitability, secretion, and possibly cel
l growth and differentiation, The gene (or genes) coding for the pore-
forming subunit of low voltage-activated channel proteins has not been
unequivocally identified. We have used reverse transcription-PCR to i
dentify partial clones from rat atrial myocytes that share high homolo
gy with a member of the E class of calcium channel genes, Antisense ol
igonucleotides targeting one of these partial clones (raE1) specifical
ly block the increase in T-current density that normally results when
atrial myocytes are treated with insulin-like growth factor I (IGF-1),
Antisense oligonucleotides targeting portions of the neuronal rat alp
ha(1E) sequence, which are not part of the clones detected in atrial t
issue, also block the IGF-l-induced increase in T-current, suggesting
that the high homology to alpha(1E) seen in the partial clone may be p
resent in the complete atrial sequence. The basal T-current expressed
in these cells is also blocked by antisense oligonucleotides, which is
consistent with the notion that IGF-1 up-regulates the same gene that
encodes the basal current, These results support the hypothesis that
a member of the E class of calcium channel genes encodes a low voltage
-activated calcium channel in atrial myocytes.