Voltage gated calcium channels in molluscs: classification, Ca2+ dependent inactivation, modulation and functional roles

Abstract

Molluscan neurons and muscle cells express transient (T-type like) and sustained LVA calcium channels, as well as transient and sustained HVA channels. In addition weakly voltage sensitive calcium channels are observed. In a number of cases toxin or dihydropyridine sensitivity justifies classification of the HVA currents in L, N or P-type categories. In many cases, however, pharmacological characterization is still preliminary. Characterization of novel toxins from molluscivorous Conus snails may facilitate classification of molluscan calcium channels. Molluscan 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 channel, through dephosphorylation by calcium dependent phosphatases or through calcium dependent disruption of connections with the cytoskeleton. Transmitter modulation operating through various second messenger mediated pathways is well documented. In general, phosphorylation through PKA, cGMP dependent PK or PKC facilitates the calcium channels, while 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 sustained LVA channels in pacemaking and the generation of firing patterns, and on the role of HVA channels in the dynamic changes in action potentials during spiking, the regulation of the release of transmitters and hormones, and the regulation of growth cone behavior and neurite outgrowth. The accessibility of molluscan preparations (e.g. the squid giant synapse for excitation release studies, Helisoma B5 neuron for neurite and synapse formation) and the large body of knowledge on electrophysiological properties and functional connections of identified molluscan neurons (e.g. sensory neurons, R15, egg laying hormone producing cells, etc.) creates valuable opportunities to increase the insight into the functional roles of calcium channels.

Expression and Modulation of an Invertebrate Presynaptic Calcium Channel α1 Subunit Homolog

“…When coexpressed with rat ␤ 1b and ␣ 2 -␦, the functional properties of the modified LCa v 2a-5ЈrbA calcium channel resemble in many ways those of mammalian N-type calcium channels showing similar activation and inactivation behavior, preferential permeation of barium over calcium, a lack of pronounced calcium-dependent inactivation, and complete block by cadmium ions. Consistent with what has been reported for native Lymnaea calcium currents in neurons (24,25), the LCa v 2a-5ЈrbA channel is insensitive to micromolar concentrations of -conotoxin GVIA and does not have characteristics of L-type channels with regard to nifedipine sensitivity. As expected from the lack of an identifiable syntaxin binding site (21), the coexpression of the channel with Lymnaea syntaxin1 did not affect channel function.…”

The Neuromuscular Junctions of the Slow and the Fast Excitatory Axon in the Closer of the CrabEriphia spinifronsAre Endowed with Different Ca2+Channel Types and Allow Neuron-Specific Modulation of Transmitter Release by Two Neuropeptides

“…The -toxins have also been widely used for the classification of invertebrate channels, including those of crustaceans. However, because no Ca 2ϩ channel has yet been sequenced in crustaceans, and the molecular and electrophysiological correspondence to the vertebrate subtype profiles is not established (for review, see Kits and Mansvelder, 1996;Skeer et al, 1996;Jeziorski et al, 2000), one should be cautious in applying the mammalian channel classification. Invertebrate Ca 2ϩ channels, defined only by pharmacological criteria derived from mammalian studies, may be reclassified when differences in their peptide sequence become apparent.…”

“…There is evidence for L-, N-, P/Q-, or T-like channels in molluscs (for review, see Kits and Mansvelder, 1996), insects (for review, see Wicher et al, 2001), and crustaceans (Araque et al, 1994;Blundon et al, 1995;Chrachri, 1995;Wright et al, 1996;Hong and Lnenicka, 1997;Hurley and Graubard, 1998;GarciaColunga et al, 1999). In crayfish, additional subtypes are present that are pharmacologically different from channels characterized in vertebrate neurons (Richmond et al, 1995(Richmond et al, , 1996Hong and Lnenicka, 1997).…”

“…Modulation of Ca 2ϩ channels by peptides occurs mainly through phosphorylation downstream of the activation of G-protein-dependent or -independent cascades (for review, see Dolphin, 1995;Kits and Mansvelder, 1996;Meir et al, 1999) or direct gating of channels (Cottrell, 1997). Generally, the major target for the modulation in invertebrates and vertebrates are neuronal N-type, in some cases also P/Q-type, but not T-type channels (Kits and Mansvelder, 1996;Wu and Saggau, 1997;Sun and Dale, 1999).…”

“…Generally, the major target for the modulation in invertebrates and vertebrates are neuronal N-type, in some cases also P/Q-type, but not T-type channels (Kits and Mansvelder, 1996;Wu and Saggau, 1997;Sun and Dale, 1999). In crustacean muscle fibers, L-type Ca 2ϩ channels are one target of postsynaptic peptidergic modulation.…”