This book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.

Ideal for graduate and undergraduate courses, the book includes PC and Macintosh versions of two programs for simulating and manipulating any aspect of synaptic transmission."--BOOK JACKET.

Cellular and Molecular Neurophysiology, Fifth Edition is the only up-to-date textbook on the market that focuses on the molecular and cellular physiology of neurons and synapses. Hypothesis-driven rather than a dry presentation of the facts, the book promotes a real understanding of the function of nerve cells that is useful for practicing neurophysiologists and students in graduate-level courses on the topic alike. This new edition explains the molecular properties and functions of excitable cells in detail and teaches students how to construct and conduct intelligent research experiments. The content is firmly based on numerous experiments performed by top experts in the field. The new edition contains new chapters on recording neuronal activity, iconotrophic and metabotropic receptors for sensory transduction, and a section containing exercises for further learning. This book will be a useful resource for neurophysiologists, neurobiologists, neurologists, and students taking graduate-level courses on neurophysiology. Authoritative foundational coverage of basic cellular and molecular neurophysiology Includes new chapters on recording neuronal activity, iconotrophic and metabotropic receptors for sensory transduction Provides fifteen appendices that describe how neurobiological techniques are interspersed in the text Presents enhanced coverage of new methodologies and experimental techniques

Synaptic neurotransmitter release is mediated by presynaptic voltage-gated calcium channels (VGCCs) via a tightly controlled mechanism. Naturally occurring mutations in the CACNA1A gene, which encodes the pore forming [alpha]1-subunit of P/Q-type VGCCs, can disrupt synaptic neurotransmission and lead to neurological disorders such as migraine, ataxia and epilepsy. Here, we aimed to understand how mutations linked to a severe form of migraine - familial hemiplegic migraine type 1 (FHM1) - affects neurotransmitter release in small central synapses. The effects of FHM1 mutations on both VGCC function and transmitter release are currently controversial. It is widely agreed that FHM1 mutations cause a shift to more negative potentials in the voltage activation threshold of P/Q-type channels. However, it is less understood whether this leads to a gain- or loss- of function of neurotransmitter release. We studied the effects of two particular FHM1 mutations using a combination of genetic manipulations and fluorescent imaging methods. First, in order to overcome species-specific differences in subunit expression, we attempted to express human cDNA encoding mutant VGCCs in the human neuronal-like cell line, NT2. Second, we compared synaptic neurotransmission in neuronal hippocampal cultures prepared from mice harbouring FHM1 mutations, with wild-type controls. Our results revealed that synaptic transmission was highly heterogeneous among individual synapses. However, FHM1 mutations did not have a significant effect on synaptic vesicular release. We also investigated the role of VGCCs in triggering spontaneous neurotransmission. We found that approximately 25 % of miniature excitatory post-synaptic currents were dependent on the stochastic opening of presynaptic VGCCs. Further analysis showed that the slow Ca2+ buffer EGTA blocks VGCC-dependent spontaneous and evoked release to a similar extent, suggesting that the two types of neurotransmission may share the same release machinery. Taken together these data provide new insights into the regulation of evoked and spontaneous release by presynaptic VGCCs.