Regulation of L-type Calcium Channel Current by Somatostatin in Guinea-Pig Gastric Myocytes

Regulation of L-type Calcium Channel Current by Somatostatin in Guinea-Pig Gastric Myocytes

To study the direct effect of somatostatin (SS) on calcium channel current (I<SUB>Ba</SUB>) in guinea-pig gastric myocytes, I<SUB>Ba</SUB> was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine (1μM), a L-type Ca<SUP>2+</SUP> channel blocker, inhibited I<SUB>Ba</SUB> by 98&#8273;1.9% (n=5), however I<SUB>Ba</SUB> was decreased in a reversible manner by application of SS. The peak I<SUB>Ba</SUB> at 0 mV were decreased to 95&#8273;1.1, 92&#8273;1.9, 82&#8273;4.0, 66&#8273;5.8, 10&#8273;2.9% at 10<SUP>&#8291;10</SUP>, 10<SUP>&#8291;9</SUP>, 10<SUP>&#8291;8</SUP>, 10<SUP>&#8291;7</SUP>, 10<SUP>&#8291;5</SUP> M of SS, respectively (n=3∼6; mean&#8273;SEM). The steady-state activation and inactivation curves of I<SUB>Ba</SUB> as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation (V<SUB>0.5</SUB>) was &#8291;12&#8273;0.5 mV in control and &#8291;11&#8273;1.9 mV in SS treated groups (respectively, n=5). The same values of half-inactivation were &#8291;35&#8273;1.4 mV and &#8291;35&#8273;1.9 mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of I<SUB>Ba</SUB> by SS. Inhibitory effect of SS on I<SUB>Ba</SUB> was significantly reduced by either dialysis of intracellular solution with GDP<SUB>β</SUB>S, a non-hydrolysable<FONT COLOR=PURPLE><SPAN STYLE= font-size:11pt; > </SPAN>G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current (VDCC<SUB>L</SUB>) via PTX- sensitive signaling pathways in guinea-pig antral circular myocytes.