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  • Sinnegger-Brauns, MJ (author)

Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca2+ channels

  • Article/chapterEnglish2004

Publisher, publication year, extent ...

  • 2004

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:d6069e69-5628-4ae0-8ef7-be2f4599e5be
  • https://lup.lub.lu.se/record/277260URI
  • https://doi.org/10.1172/JCI200420208DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Ca(v)1.2 and Ca(v)1.3 L-type Ca2+ channels (LTCCs) are believed to underlie Ca2+ currents in brain, pancreatic beta cells, and the cardiovascular system. In the CNS, neuronal LTCCs control excitation-transcription coupling and neuronal plasticity. However, the pharmacotherapeutic implications of CNS LTCC modulation are difficult to study because LTCC modulators cause card iovascular (activators and. blockers) and neurotoxic (activators) effects. We selectively eliminated high dihydropyridine (DHP) sensitivity from Ca(v)1.2 alpha1 subunits (Ca(v)1.2DHP(-/-)) without affecting function and expression. This allowed separation of the DHP effects of Ca(v)1.2 from those of Ca(v)1.3 and other LTCCs. DHP effects on pancreatic P cell LTCC currents, insulin secretion, cardiac inotropy, and arterial smooth muscle contractility were lost in Ca(v)1.2DHP(-/-) mice, which rules out a direct role of Ca(v)1.3 for these physiological processes. Using Ca(v)1.2DHP(-/-) mice, we established DHPs as mood-modifying agents: LTCC activator-induced neurotoxicity was abolished and disclosed a depression-like behavioral effect without affecting spontaneous locomotor activity. LTCC activator BayK 8644 (BayK) activated only a specific set of brain areas. In the ventral striatum, BayK-induced release of glutamate and 5-HT, but not dopamine and noradrenaline, was abolished. This animal model provides a useful tool to elucidate whether Ca(v)1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Hetzenauer, A (author)
  • Huber, IG (author)
  • Renström, ErikLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)mphy-ere (author)
  • Wietzorrek, G (author)
  • Berjukov, S (author)
  • Cavalli, M (author)
  • Walter, D (author)
  • Koschak, A (author)
  • Waldschutz, R (author)
  • Hering, S (author)
  • Bova, S (author)
  • Rorsman, PatrikLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-pro (author)
  • Pongs, O (author)
  • Singewald, N (author)
  • Striessnig, J (author)
  • Diabetes - öpatofysiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Journal of Clinical Investigation113:10, s. 1430-14390021-9738

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