The modulation of [Ca2+]i by parathyroid hormone (PTH) has been extensively studied in vertebrates. The present study examined the effects of PTH on [Ca2+]i in isolated invertebrate neurons B5 from buccal ganglia of the pond snail, Helisoma trivolvis, utilizing the Fura-2 fluorescence technique. Bovine PTH, bPTH-(1-84), induced a slow and sustained increase in [Ca2+]i in neurons B5. In contrast, the elevation of extracellular K+ concentration from 1.7 mM to 15 mM induced a rapid and transient increase in [Ca2+]i. Simultaneous application of 15 mM KCl and bPTH-(1-84), or application of 15 mM KCl in the presence of bPTH-(1-84) additively increased [Ca2+]i in neurons B5. An increase in [Ca2+]i in neurons B5 was also induced by a PTH agonist [bPTH-(1-34)], but not by a PTH antagonist [bPTH-(3-34)]. The absence of calcium, or the presence of lanthanum (2 mM) or omega-conotoxin (10 microM), in the bath solution abolished the effect of bPTH-(1-84) on [Ca2+]i. Furthermore, our results demonstrated that the effect of PTH on [Ca2+]i in neurons B5 was not due to the hormonal modulation of voltage-dependent Na+ or K+ channels or a Na+/Ca2+ exchanger. The results from this study show that PTH can modulate [Ca2+]i in an identified invertebrate neuron mainly by promoting extracellular calcium influx via the N-like voltage-dependent calcium channel.