VOLTAGE-GATED CALCIUM CHANNELS IN MOLLUSKS - CLASSIFICATION, CA2+ DEPENDENT INACTIVATION, MODULATION AND FUNCTIONAL ROLES

Molluscan neurons and muscle cells express transient (T-type like) and sustained LVA calcium channels, as well as transient and sustained HV A channels. In addition weakly voltage sensitive calcium channels are observed. In a number of cases toxin or dihydropyridine sensitivity ju stifies classification of the HVA currents in L, N or P-type categorie s. In many cases, however, pharmacological characterization is still p reliminary. Characterization of novel toxins from molluscivorous Conus snails may facilitate classification of molluscan calcium channels. M olluscan preparations have been very useful to study calcium dependent inactivation of calcium channels. Proposed mechanisms explain calcium dependent inactivation through direct interaction of Ca2+ with the ch annel, through dephosphorylation by calcium dependent phosphatases or through calcium dependent disruption of connections with the cytoskele ton. Transmitter modulation operating through various second messenger mediated pathways is well documented. In general, phosphorylation thr ough PKA, cGMP dependent PK or PKC facilitates the calcium channels, w hile putative direct G-protein action inhibits the channels. Ca2+ and cGMP may inhibit the channels through activation of phosphodiesterases or phosphatases. Detailed evidence has been provided on the role of s ustained LVA channels in pacemaking and the generation of firing patte rns, and on the role of KVA channels in the dynamic changes in action potentials during spiking, the regulation of the release of transmitte rs and hormones, and the regulation of growth cone behavior and neurit e outgrowth. The accessibility of molluscan preparations (e.g. the squ id giant synapse for excitation release studies, Helisoma B5 neuron fo r neurite and synapse formation) and the large body of knowledge on el ectrophysiological properties and functional connections of identified molluscan neurons (e.g. sensory neurons, R15, egg laying hormone prod ucing cells, etc.) creates valuable opportunities to increase the insi ght into the functional roles of calcium channels.