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Multiple second-messenger system modulation of voltage-activated calcium currents in teleost retinal horizontal cells

C L Pfeiffer-Linn1, E M Lasater

  • 1John Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.

Journal of Neurophysiology
|July 11, 1998
PubMed

Insights

Dopamine activates two second-messenger systems, cyclic AMP and diacylglycerol, in white bass horizontal cells. These pathways modulate calcium currents by protein phosphorylation, decreasing transient currents and increasing sustained currents.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Biochemistry

Background:

  • White bass horizontal cells possess two distinct voltage-activated calcium currents: T-type and sustained.
  • These calcium currents are crucial for neuronal function and are subject to modulation by intracellular signaling pathways.

Purpose of the Study:

  • To investigate the modulation of T-type and sustained calcium currents by different second-messenger systems.
  • To elucidate the roles of cyclic AMP (cAMP) and diacylglycerol (DAG) pathways in regulating calcium currents.
  • To determine the involvement of protein kinases A (PKA) and C (PKC) in these modulatory processes.

Main Methods:

  • Patch-clamp electrophysiology to measure voltage-activated calcium currents.
  • Application of specific agonists (dopamine) and inhibitors (staurosporine, cAMP-dependent protein kinase inhibitor) to activate/block second-messenger pathways.
  • Analysis of protein phosphorylation as a mechanism of modulation.

Main Results:

  • Both cAMP and DAG pathways significantly decreased transient calcium currents and increased sustained currents.
  • The cAMP pathway activated PKA, while the DAG pathway activated PKC.
  • Low-concentration inhibitors showed specificity: staurosporine for PKC and cAMP-dependent protein kinase inhibitor for PKA.
  • Dopamine activated both pathways, leading to additive modulatory effects on calcium currents.

Conclusions:

  • Two independent second-messenger systems (cAMP and DAG) converge to produce similar modulatory effects on distinct calcium currents in horizontal cells.
  • Protein phosphorylation by PKA and PKC mediates these modulatory actions.
  • Dopamine can initiate multiple signaling cascades to fine-tune neuronal excitability via calcium current modulation.

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