ANTISENSE OLIGONUCLEOTIDES AGAINST RAT-BRAIN ALPHA(1E) DNA AND ITS ATRIAL HOMOLOG DECREASE T-TYPE CALCIUM CURRENT IN ATRIAL MYOCYTES

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.