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This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/H829    most recent 00411.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Larsen, J. K. Articles by Best, P. M. Search for Related Content PubMed PubMed Citation Articles by Larsen, J. K. Articles by Best, P. M.

Disruption of growth hormone secretion alters Ca²⁺ current density and expression of Ca²⁺ channel and insulin-like growth factor genes in rat atria

¹Department of Molecular and Integrative Physiology and ²College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois

Submitted 3 May 2004 ; accepted in final form 6 October 2004

The influence of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis on expression of low-voltage-activated (LVA) Ca²⁺ current in atrial tissue was investigated using spontaneous dwarf (SpDwf) rats, a mutant strain that lacks GH. Atrial myocytes from SpDwf rats express LVA and high-voltage-activated (HVA) Ca²⁺ currents and the Ca²⁺ channel ₁-subunit genes Ca_V1.2, Ca_V2.3, Ca_V3.1, and Ca_V3.2. LVA current density decreases significantly beginning at, or shortly after, birth in normal animals; however, its density is maintained in SpDwf rats at 1 pA/pF for 12 wk after birth. The abundance of mRNAs encoding Ca_V2.3 and Ca_V3.2 declines with advancing age in normal atrial development, yet expression of Ca_V2.3 mRNA remains significantly elevated in older SpDwf animals. Quantitation of local transcript levels for mRNAs encoding IGF-I and IGF-I receptor (IGF-IR) also reveals significant differences in expression of these transcripts in atrial tissue of SpDwf animals compared with controls. In SpDwf rats, the abundance of IGF-IR mRNA remains elevated at many postnatal ages, whereas mRNA encoding IGF-I is maintained only in older animals. Physiological concentrations of IGF-I cause two- to threefold increases in LVA current density in primary cultures of atrial myocytes, and this effect is blocked by an antisense oligonucleotide targeting the IGF-IR. Thus disruption of GH production in SpDwf animals alters expression of atrial LVA Ca²⁺ channel and IGF genes as well as postnatal regulation of LVA Ca²⁺ current density, most likely acting through compensatory mechanisms via the local IGF-IR.

low-voltage-activated calcium current; electrophysiology; spontaneous dwarf rats; quantitative reverse transcription-polymerase chain reaction