Inhibition of recombinant human cardiac L-type Ca2+ channel α(1C) subunits by 3-isobutyl-1-methylxanthine

Ian M. Fearon, Adrian C.V. Palmer, Anthony J. Balmforth, Stephen G. Ball, Gabor Mikala, Chris Peers

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Inhibition of ion channels by the phosphodiesterase inhibitor 3- isobutyl-1-methylxanthine (IBMX) and related compounds has been demonstrated in various cell types, including the neuromuscular junction, GH3 cells and vascular smooth muscle cells. These effects may be unrelated to the actions of these compounds on cellular metabolism, intracellular Ca2+ stores and phosphodiesterase inhibition. In this study, the inhibition of recombinant human cardiac L-type Ca2+ channel α(1C) subunits by IBMX was examined using the whole-cell configuration of the patch clamp technique. Inhibition was repeatable, voltage-independent and associated with increased apparent channel inactivation. The actions of IBMX were unaffected in the presence of inhibitors of protein kinases A and G. The non-xanthine phosphodiesterase inhibitor rolipram had a small inhibitory effect on currents, but this was also unaffected by a protein kinase A inhibitor. These effects of IBMX could not be attributed to release of Ca2+ from intracellular stores. Our findings indicate that methylxanthines can inhibit the cardiac L-type Ca2+ channel α(1C) subunit in the absence of auxiliary subunits by an undetermined, possibly direct mechanism.

Original languageEnglish
Pages (from-to)353-358
Number of pages6
JournalEuropean Journal of Pharmacology
Volume342
Issue number2-3
DOIs
Publication statusPublished - Jan 26 1998

Keywords

  • Ca channel
  • Cyclic nucleotide
  • Isobutylmethylxanthine
  • Phosphodiesterase

ASJC Scopus subject areas

  • Pharmacology

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