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Norepinephrine acts on the KATP channel and produces different effects on [Ca2+]i in oscillating and non-oscillating

T Schermerhorn1, G W Sharp

  • 1Department of Molecular Medicine, College of Veterinary Medicine, Cornell University Ithaca, New York 14853, USA.

Cell Calcium
|September 28, 2000
PubMed

Insights

Norepinephrine (NE) inhibits insulin secretion by reducing intracellular calcium. This effect is mediated by KATP channel activation, though NE impacts oscillating and non-oscillating cells differently.

Area of Science:

  • Endocrinology
  • Cell Physiology
  • Neuropharmacology

Background:

  • Norepinephrine (NE) is known to inhibit insulin secretion.
  • This inhibition is partly attributed to a decrease in intracellular free calcium ([Ca2+]i).
  • HIT-T15 cells exhibit distinct calcium oscillation patterns in response to glucose.

Purpose of the Study:

  • To investigate the precise effects of NE on intracellular calcium ([Ca2+]i) in individual HIT-T15 cells.
  • To differentiate the impact of NE on calcium dynamics in oscillating versus non-oscillating cells.
  • To elucidate the specific ion channel mechanisms underlying NE's action on [Ca2+]i.

Main Methods:

  • Utilized indo 1 dye to measure [Ca2+]i in individual HIT-T15 cells.
  • Categorized cells into oscillators and non-oscillators based on glucose-induced calcium responses.
  • Administered NE and measured its effects on basal and stimulated [Ca2+]i, including responses to KCl and diazoxide.

Main Results:

  • NE decreased [Ca2+]i in non-oscillating cells.
  • In oscillating cells, NE reduced both the amplitude and frequency of calcium oscillations.
  • The inhibitory effect of NE on [Ca2+]i was mediated by the activation of ATP-sensitive potassium (KATP) channels.

Conclusions:

  • NE decreases intracellular calcium ([Ca2+]i) in both oscillating and non-oscillating HIT-T15 cells via KATP channel activation.
  • Despite a common mechanism, NE exhibits differential effects on the calcium dynamics of oscillating versus non-oscillating cells.
  • These findings highlight the complex regulation of insulin secretion by norepinephrine.

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