INVESTIGATION OF THE EFFECT OF INTRACELLULAR CALCIUM ON THE CAMP-MEDIATED INCREASE IN THE CALCIUM CURRENT

The experiments were conducted on intracellularly persfused neurons of the mollusk Helix pomatia, in which a serotonin (5-HT)-induced increase in the calcium current (I(Ca)), mediated by cAMP, is observed. It was established that desensitization of the cell to the action of 5-HT is due to an increase in the intracellular Ca2+ concentration ([Ca 2+]i). At [Ca2+]i = 10(-7) and 10(-6) M, the effect of 5-HT constituted 60 and 32% of this value in the control (in the presence of 10 mM EGTA in the intracellular solution), respectively; at [Ca2+]i = 10(-5) M, there was no effect of 5-HT at all. The addition of the calmodulin antagonist trifluoperazine (5.-10(-5) mM) or blockers of phosphodiesterase (5 mM theophylline or 10(-4) M IBMX) to the perfusate sharply weakened the ability of calcium to inhibit the effect of 5-HT; at [Ca2+]i = 10(-5) M, in the presence of one of these compounds, the effect constituted 60-70% of its control value. It is concluded that the calcium-calmodulin-dependent phosphodiesterase is a key link in the interaction of the two-signal transduction pathway - Ca2+ and cAMP in modulation of the calcium-channel activity.