Na+/Ca2+ exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility

Kazuhiro Nishiyama, Yasu Taka Azuma, Satomi Kita, Naoki Azuma, Satomi Hayashi, Hidemitsu Nakajima, Takahiro Iwamoto, Tadayoshi Takeuchi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The Na+/Ca2+ exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca2+ concentrations. NCX is critical for Ca2+ regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. To determine the role of NCX1 and NCX2 in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced responses in the longitudinal smooth muscle of the distal colon in NCX1 and NCX2 double-heterozygote knockout mice (Double HET). We found that the amplitudes of EFS-induced relaxation that persisted during EFS were greater in Double HET than in wild-type mice (WT). Under the non-adrenergic, non-cholinergic (NANC) condition, EFS-induced relaxation in Double HET was similar in amplitude to that of WT. In the experiments in which l-NNA was added under NANC conditions following the EFS, the magnitudes of EFS-induced relaxation were smaller in Double HET than those in WT. In addition, an NCX inhibitor, SN-6, enhanced EFS-induced relaxation but did not affect EFS-induced relaxation under NANC condition, as in Double HET. Moreover, the magnitudes of relaxation induced by NOR-1, which generates NO, were greater in Double HET compared with WT. Similarly, SN-6 potentiated the magnitudes of NOR-1-induced relaxation. In this study, we demonstrate that NCX regulate colonic motility by altering the sensitivity of the inhibitory component.

Original languageEnglish
Pages (from-to)235-245
Number of pages11
JournalJournal of Pharmacological Sciences
Volume123
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Na<sup>+</sup>/Ca<sup>2+</sup> exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility'. Together they form a unique fingerprint.

Cite this