An increase in the intracellular [Ca²⁺] is a key signal in the stimulus-secretion coupling of insulin from the pancreatic β-cell. This results from influx through voltage-gated L-type Ca²⁺ channels, which are activated during action potential electrical activity elicited in response to secretagogues such as glucose. Somatostatin (SRIF) is a potent inhibitor of insulin secretion. This is mediated by the sst₅ receptor and is primarily achieved via the combined activation of K_ATP and GIRK channels. These act to hyperpolarize the membrane potential, inhibit electrical activity and reduce Ca²⁺ influx (Smith et al. 2001). The specific sst₁ receptor agonist CH-275 also inhibits electrical activity in the β-cell (Smith et al. 2001). Since this effect is accompanied by an increase in input resistance, with no associated hyperpolarization of membrane potential, it is unlikely to be mediated by K⁺ channel activation, but more likely to result from a direct inhibition of Ca²⁺ channel activity. To investigate this possibility, the effect of SRIF on Ca²⁺ currents was studied in MIN-6 cells, a mouse β-cell line, using the perforated-patch whole-cell technique (Dalle et al. 1999; Smith et al. 2001). Experiments were performed at 32 °C. Data were discarded if the series conductance was < 40 nS. Currents were elicited by voltage steps, 250-500 ms in duration applied at 0.1 Hz, positive to the holding potential of -70 mV. Currents were confirmed to be flowing solely through L-type Ca²⁺ channels being abolished by 20 µM nifedipine. Data are quoted as means ± S.E.M. (n is the number of determinations).

SRIF reversibly inhibited Ca²⁺ currents in a voltage-independent manner, with an EC₅₀ of 8.4 ± 3.4 nM and a maximal inhibition of 22 ± 5 % (n = 4). The effects of 100 nM SRIF were mimicked by 100 nM CH-275, whereas neither 100 nM BIM-23027, nor L-662, 855 (selective agonists at the sst_2/3 and sst₅ receptors, respectively) had a significant effect (ANOVA) relative to control. In conclusion, SRIF can reduce glucose-induced electrical activity in MIN-6 cells by inhibition of L-type Ca²⁺ currents. Studies with selective agonists and antagonists are consistent with this effect being mediated by the sst₁ receptor.

Dalle, S., Smith, P., Le-Nguyen, D., Le Brigand, L., Bergeron, F., Ashcroft, F.M. & Bataille, D. (1999). J. Biol. Chem. 274, 10869-10876.

Smith, P.A., Sellers, L.A. & Humphrey, P.P.A. (2001). J. Physiol. 532, 127-142. abstract