Different types of calcium channels mediate central synaptic transmission

Abstract

Synaptic transmission is mediated by calcium entry through voltage-dependent calcium channels in presynaptic nerve terminals. Various types of calcium channel have been characterized in neuronal somata, but it is not clear which subtypes induce transmitter release at central synapses. The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTx) suppresses the excitatory postsynaptic responses only partially, whereas potassium-induced release of glutamate from brain synaptosomes can be blocked by omega-Aga-VIA (ref. 9), a blocker of P-type calcium channels and possibly of other types of calcium channels. Here we test type-specific calcium-channel blockers on postsynaptic currents recorded from neurons in thin slices of rat central nervous system. Inhibitory postsynaptic currents in cerebellar and spinal neurons and excitatory postsynaptic currents in hippocampal neurons are markedly suppressed by omega-Aga-IVA and reduced to a lesser extent by omega-CgTx. The L-type calcium channel blocker nicardipine had no effect. Our results indicate that at least two types of calcium channel mediate synaptic transmission in the mammalian central nervous system.

Cellular and Molecular Mechanisms Underlying Learning and Memory Impairments Produced by Cannabinoids: Figure 1.

“…nels is known to be required for release of transmitter from hippocampal synapses (Takahashi and Momiyama 1993;Wheeler et al 1994). To test the hypothesis that cannabinoids mediate their effects on transmission in the hippocampus by inhibiting N-and P/Q-type calcium channels, the effects of cannabinoid receptor activation were measured before and after pharmacological blockade of these channels (Sullivan 1999).…”

Alternative Splicing of the β4Subunit Has α1Subunit Subtype-Specific Effects on Ca2+Channel Gating

“…These genes encode large pore-forming proteins (Ͼ2200 amino acids) that are differentially distributed throughout the nervous system (Westenbroek et al, 1990(Westenbroek et al, , 1998. Synaptic N-, P/Q-, and R-type channels, formed by ␣ 1B , ␣ 1A , and ␣ 1E subunits, respectively, play a principal role in regulating neurotransmitter release (Turner et al, 1992;Takahashi and Momiyama, 1993;Wheeler et al, 1994;Wu et al, 1999).Ca 2ϩ channel ␤ subunits (subtypes 1-4) are highly homologous intracellular proteins with primary sequences ranging from 480 to 630 amino acids (for review, see Birnbaumer et al, 1998). The sequence can be divided into five domains on the basis of the regions of amino acid identity between subtypes.…”

Effect of calcium channel blockers on stress-induced visceral, endocrinological and immune responses

“…The observed effect of nimodipine and flunarizine on immune parameters could be due to their increased selectivity for the CNS (34,35). The L-, N-and P/Q-type calcium channels reportedly play a pivotal role in mediating calcium influx that triggers depolarization evoked neurotransmitter release in nerve terminals (12,13). It has been shown that neuronal communication of lymphoid tissue is possible and this may be an important route which allows functional interaction between the CNS and the immune system.…”

“…Sensory neurons have been shown to possess 5 distinct types of voltage dependent Ca 2~ channels designated as L, N, T, P and Q. The L, Nand P/Q-type Ca 2. channels have been implicated to play .an important role in mediating Ca 2 § influx that triggers depolarization evoked neurotransmitter release from nerve terminals (12,13). Calcium channel blockers (CCBs) are the agents which block the entry of Ca 2. into the cell by interacting with voltage-dependent Ca 2. channels.…”