[Updated on Apr. 18] Integration of CiNii Articles into CiNii Research

Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes

  • IMOTO Keisuke
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan
  • ARATANI Momoko
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan
  • KOYAMA Takahiro
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan
  • OKADA Muneyoshi
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan
  • YAMAWAKI Hideyuki
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan

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Abstract

<p>Expression of thrombospondin-4 (TSP-4), a matricellular protein, is increased in the heart tissue of various cardiac disease models. In dorsal root ganglion neurons, TSP-4 inhibits L-type Ca2+ channel (LTCC) activity. Although TSP-4 might be related to the electrophysiological properties in heart, it remains to be clarified. The present study aimed to clarify the effects of TSP-4 on action potential (AP), LTCC current (ICaL) and voltage-dependent K+ (Kv) channel current (IKv) in rat isolated ventricular myocytes by a patch clamp technique. Ventricular myocytes were isolated from the heart of adult male Wistar rats. The ventricular myocytes were treated with TSP-4 (5 nM) or its vehicle for 4 hr. Then, whole-cell patch clamp technique was performed to measure AP (current-clamp mode) and ICaL and IKv (voltage-clamp mode). The mRNA expression of Kv channels was examined by reverse transcription-polymerase chain reaction. TSP-4 had no effect on the resting membrane potential and peak amplitude of AP. On the other hand, TSP-4 significantly prolonged AP duration (APD) at 50% and 90% repolarization. TSP-4 significantly inhibited the peak amplitudes of ICaL and IKv. TSP-4 had no effect on mRNA expression of Kv channels (Kcna4, Kcna5, Kcnb1, Kcnd2 and Kcnd3). The present study for the first time demonstrated that TSP-4 prolongs APD in rat ventricular myocytes, which is possibly mediated through the suppression of Kv channel activity.</p>

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