Ls. Satin et al., CONTRIBUTION OF L-AND NON-L-TYPE CALCIUM CHANNELS TO VOLTAGE-GATED CALCIUM CURRENT AND GLUCOSE-DEPENDENT INSULIN-SECRETION IN HIT-T15 CELLS, Endocrinology, 136(10), 1995, pp. 4589-4601
The pharmacological properties of voltage-gated Ca current and glucose
-dependent insulin secretion were determined using the HIT insulinoma
line to understand the role of Ca channels in stimulus-secretion coupl
ing. The L-type Ca channel antagonist nimodipine inhibited a maximum o
f 50-55% of the peak Ca current, suggesting that L- and non-L-type cha
nnels contribute to Ca current. The L-agonist BAY K 8644 increased Ca
current by 155%, whereas the N-channel blocker omega-conotoxin MVIIA r
eversibly blocked 35% of the peak Ca current. Total block with nimodip
ine and MVIIA was additive. Conotoxin MVIIC did not affect HIT Ca curr
ent. Prolonged depolarizations elicited rapidly and slowly inactivatin
g Ca currents. Nimodipine partially inhibited transient current, but f
ully inhibited slowly inactivating current, suggesting that the former
is mediated by L- and N-channels, and the latter is mediated by L-cha
nnels. Like slowly inactivating Ca current, glucose-dependent insulin
secretion was fully inhibited by nimodipine and insensitive to MVIIA.
BAY K potentiated secretion and antagonized nimodipine block. These re
sults suggest that persistent Ca current is mediated by L-channels and
is strongly coupled to insulin secretion, whereas transient Ca curren
t is mediated by L- and N-channels and is weakly coupled. Sustained Ca
influx may be preferentially coupled because glucose persistently dep
olarizes HIT cells and inactivates more transient Ca channel pathways.