B. Ligon et al., CLASS-A CALCIUM-CHANNEL VARIANTS IN PANCREATIC-ISLETS AND THEIR ROLE IN INSULIN-SECRETION, The Journal of biological chemistry, 273(22), 1998, pp. 13905-13911
The initiation of insulin release from rat islet beta cells relies, in
large part, on calcium influx through dihydropyridine-sensitive (alph
a(1D)) voltage-gated calcium channels. Components of calcium-dependent
insulin secretion and whole cell calcium current, however, are resist
ant to L-type channel blockade, as well as to omega-conotoxin GVIA, a
potent inhibitor of alpha(1B) channels, suggesting the expression of a
dditional exocytotic calcium channels in the islet. We used a reverse
transcription-polymerase chain reaction-based strategy to ascertain at
the molecular level whether the alpha(1A) calcium channel isoform was
also present. Results revealed two new variants of the rat brain alph
a(1A) channel in the islet with divergence in a putative extracellular
domain and in the carboxyl terminus. Using antibodies and cRNA probes
specific for alpha(1A) channels, we found that the majority of cells
in rat pancreatic islets were labeled, indicating expression of the al
pha(1A) channels in beta cells, the predominant islet cell type. Elect
rophysiologic recording from isolated islet cells demonstrated that th
e dihydropyridine-resistant current was sensitive to the alpha(1A) cha
nnel blocker, omega-agatoxin IVA. This toxin also inhibited the dihydr
opyridine-resistant component of glucose-stimulated insulin secretion,
suggesting functional overlap among calcium channel classes. These fi
ndings confirm the presence of multiple high voltage-activated calcium
channels in the rat islet and implicate a physiologic role for alpha(
1A) channels in excitation-secretion coupling in beta cells.