When was the hitchhikers guide to the galaxy made

Dominique Jackson Fook as Fook. Kelly Macdonald Reporter as Reporter. Ian McNeice Kwaltz as Kwaltz voice. Garth Jennings. Douglas Adams book screenplay Karey Kirkpatrick screenplay.

More like this. Watch options. Storyline Edit. Everyone has bad mornings. You wake up late, you stub your toe, you burn the toast, but for a man named Arthur Dent, this goes far beyond a bad day. When he learns that a friend of his is actually an alien with advanced knowledge of Earth's impending destruction, he is transported off the Earth seconds before it is blown up to make way for a new hyperspace motorway. And as if that's not enough, throw in being wanted by the Police, Earth II, an insane electronic encyclopedia, no tea whatsoever, a chronically depressed robot and the search for the meaning of life, and you've got the greatest adventure off Earth.

Don't Panic. Rated PG for thematic elements, action and mild language. Did you know Edit. Trivia The producers have stated that this movie was not a literal translation of the books just as the books were not a literal translation of the original radio show , but all of the new ideas and characters came from Douglas Adams.

The hired writer simply came aboard to improve structure and make the screenplay more coherent. Goofs When Arthur is speaking to Trillian Zooey Deschanel as she takes a shower, he briefly begins to address her by her real name Zooey , then corrects himself. Quotes The Book : In the beginning the universe was created. Crazy credits The film has effectively two title sequences.

The first is part of the opening song, when the title appears out of a screenful of bubbles as the "So Long And Thanks For All The Fish" number gears up.

The second is after the Vogon ships destroy the Earth and The Book is shown for the first time; as the original theme music of the radio show and miniseries plays, the book's spine rotates into view and reveals its, and the movie's, title. User reviews 1. Top review. Don't Panic! Douglas Adams' legacy has been turned into a delicious acid-trip of a movie, featuring love, aliens and the answer to life, the universe and everything.

Douglas Adams turned his sci-fi phenomenon, The Hitchhiker's Guide to the Galaxy into a hit radio and TV series, a five-part trilogy of novels and a BAFTA-winning computer game, but complained making it into a movie was like "trying to grill a steak by having a succession of people blow on it". After a year battle with Disney to get the film made - and a day after a planet was named after the story's protagonist Arthur Dent - Adams died of a heart attack.

Interactions between animal toxins and Na v channels. A; left Side view of a Na v channel cartoon indicating the paddle motif indicated in red as the binding site for hanatoxin from the Grammostola rosea tarantula, Magi5 from the Hexathelidae spider Macrothele gigas , and BmK M1 from the Buthus martensii Karsch scorpion. Middle Structures of the three toxins colored according to residue class green, hydrophobic; blue, positively charged; red, negatively charged; orange, polar.

Toxin backbone is also shown. Despite binding to a similar region on the Na v channel, each toxin has a different effect on channel opening or closing. Black trace represents control conditions, and red trace represents toxin.

BTX binds to the inner region of the pore to drastically modify Na v channel gating. Shown is the ability of BTX to open Na v channels at voltages where they are normally closed and to inhibit fast inactivation. TTX played an important role in the biochemical purification of the Na v channel protein Agnew et al. Moreover, structural information about TTX and STX was used to predict the diameter of the Na v channel pore, thereby providing powerful insights into the molecular organization of this ion channel family that still hold up today Woodward, ; Hille, b ; Schantz et al.

Recently, STX returned to the spotlight when fluorescent derivatives were synthesized Ondrus et al. These reagents enable real-time imaging of Na v channels in live cells at the single-molecule level. Currently, TTX is used to divide the Na v channel family into two groups based on their sensitivity toward the toxin; TTX-sensitive channel isoforms Na v 1.

Although Na v 1. Although this region of the selectivity filter plays a role in STX binding as well, other important extracellular residues have been implicated in forming the STX receptor site, most likely because of supplementary interactions with the second guanidinium group within the toxin Fozzard and Lipkind, The steroidal alkaloid BTX is found in the excretions of poison dart frogs and certain bird species Tokuyama et al.

BTX irreversibly inhibits fast and slow inactivation and shifts the voltage dependence of activation to more negative potentials, resulting in persistent Na v channel activation. In addition, toxin-modified channels have a reduced single-channel conductance and an altered ion selectivity pattern, perhaps caused by a widened selectivity filter.

The receptor site for BTX involves residues in multiple S6 pore segments and partially overlaps with that of local anesthetics Linford et al. Because of its high affinity, radioactive BTX has been used extensively for Na v channel identification in tissues and vesicles, and in screening potential therapeutics Cooper et al. The alkaloid toxin VTD is found in Liliaceae plants and causes persistent opening of Na v channels while reducing single-channel conductance Ulbricht, Evidence that the VTD and local anesthetics receptor overlap comes from mutagenesis studies within the pore-forming S6 segments, which also demonstrate that local anesthetics-occupied Na v channels do not bind VTD Ulbricht, Because of its ability to open Na v channels, VTD is used in drug-screening essays in which controlling the membrane voltage is impractical Felix et al.

Although the molecular architecture of cyclic polyether compounds from dinoflagellates such as brevetoxins and ciguatoxins is remarkable, these compounds have been implicated in numerous seafood-related poisonings and massive fish and marine mammal fatalities Lin et al. From a chemical point of view, these ladder-like polyether toxins may partition in the membrane to complement a structural motif within the Na v channel e.

In addition to their use as pharmacological tools, conotoxins are currently being tested in clinical trials as therapeutics for a range of disorders Bende et al. In addition, the net positive charge on these peptides indeed allows them to participate in long-range electrostatic interactions over realistic distances, which can contribute to binding and to the blocking of ion conduction Hui et al.

Detailed investigations on KIIIA revealed that this peptide can trap TTX in its binding site such that the guanidinium toxin cannot dissociate from the channel until the peptide does. As a result, these compounds could serve as an antidote in life-threatening situations involving guanidinium toxin poisoning Zhang et al. Also, a sufficient diversity of conotoxins has been identified to assemble a pharmacological kit for distinguishing various Na v channel isoforms in mammalian cells Zhang et al.

In general, gating-modifier toxins interact with the S3b—S4 helix-turn-helix motif or paddle motif within each of the four Na v channel VSDs Gilchrist et al. The pharmacological importance of this distinct region was first established in K v channels where mutations in the S3b—S4 loop altered channel sensitivity to hanatoxin, a founding member of the K v channel gating modifier toxin family Li-Smerin and Swartz, Later, this S3b—S4 motif was also identified in each of the four Na v channel VSDs, and transplanting these regions from insect or mammalian Na v to K v channels resulted in functional K v channels that are sensitive to Na v channel toxins Bosmans et al.

Based on the resulting functional effects, Na v channel scorpion toxins were divided into two classes Couraud et al. Although their functional effects indeed imply a primary interaction with the DIV voltage sensor S3b—S4 paddle, antibody and photo-affinity—labeling studies as well as mutagenesis experiments on rNa v 1. However, a study by Campos et al. As a result of toxin exposure, the response of the channel to a subsequent depolarization may be enhanced, thereby resulting in a shift of the voltage dependence of activation to more negative voltages.

The list of Na v channel spider toxins with comparable functionally important surfaces is growing rapidly, mostly because of the application of novel and sensitive screening techniques Terstappen et al. Interestingly, structure—function studies on SGTx1 from the Scodra griseipes tarantula with K v channels and Magi5 from the hexathelid spider Macrothele gigas with Na v channels reveal the functional importance of a cluster of hydrophobic residues surrounded by charged residues Lee et al.

As a result of this amphipathic character, spider toxins are thought to partition in the membrane to interact with their receptor site within Na v channel and K v channel voltage sensors Milescu et al.

Although more experiments are required to clarify the influence of membrane lipids on toxin sensitivity of Na v channels, it is not unreasonable to assume that spider toxins with comparable structures do not necessarily have similar membrane-interacting properties that may help determine their potency or target specificity Gupta et al.

Depending on which VSDs they target and how those sensors couple to the overall Na v channel gating process, spider toxins can have three distinct effects on Na v channel function Bosmans and Swartz, The first is for the toxin to inhibit channel opening in response to membrane depolarization Middleton et al.

A second outcome is for the toxin to hinder fast inactivation Wang et al. Finally, the toxin can facilitate opening of the channel by shifting Na v channel activation to hyperpolarized voltages Corzo et al. After transferring S3b—S4 motifs within each of the four Na v channel voltage sensors into K v channels to individually examine their interactions with toxins Bosmans et al.

Mutagenesis studies have shown that cationic residues within sea anemone toxins are responsible for affinity differences between various Na v channel isoforms Barhanin et al. Typically, these toxins enhance recovery from inactivation without affecting Na v channel activation, deactivation, or closed-state inactivation Hanck and Sheets, Interestingly, sea anemone toxins bind with the highest affinity to the closed state of Na v channels.

This is surprising, as these peptides are generally hydrophilic in nature, and their binding site on the domain IV voltage sensor may be buried in the lipid membrane when the channel is closed. To reach their target, sea anemone toxins would therefore have to partition into the membrane, a feature observed with several spider toxins Smith et al.

Cone snail venom contains toxins that alter Na v channel gating by interacting with their voltage sensors. Given their preference for the nociceptive channel Na v 1. Instead, they inhibit Na v channel fast inactivation, resulting in a prolongation of the action potential. Finally, I-conotoxins shift Na v channel activation to more hyperpolarized potentials, thereby causing these channels to open at voltages where they are normally closed Buczek et al.

Pompilidotoxins are small peptides purified from the venom of wasps that slow fast inactivation of neuronal Na v channels but not Na v 1. Site-directed mutagenesis of Na v 1. In concert, cationic residues within the pompilidotoxins were found to be critical for toxin activity Konno et al.

Because their chemical synthesis is relatively straightforward, these toxins are valuable tools to study Na v channel gating. Na v channels have played the role of biophysical muse for generations of membrane biophysicists. This has in turn driven fundamental advances on both experimental and theoretical fronts, and the future remains bright as new chemical and theoretical approaches are applied to every aspect of Na v channel biology and pharmacology.

The diversity of natural toxins that affect Na v channel function will help elucidate the basics of channel gating while their therapeutic promise continues to develop. Moreover, the discovery of small-molecule compounds that bind to voltage sensors also represents an important development for isoform-specific therapeutics McCormack et al.

The development of chemical probes that report on activation and inactivation gating will produce new insights into function and will allow for a comparison of bacterial and eukaryotic Na v channels. Furthermore, as these membrane proteins enter the new cryo—electron microscopy structural era, there is now the real possibility that Na v channel aficionados will have high resolution structural data on eukaryotic Na v channels to spark new predictions and validate old ones, as well as to inspire a new generation of excitable investigators.

Payandeh is an employee of Genentech. National Center for Biotechnology Information , U. Journal List J Gen Physiol v. J Gen Physiol. Christopher A. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to Christopher A. Ahern: ude. Received Aug 6; Accepted Nov This article has been cited by other articles in PMC. Abstract Eukaryotic voltage-gated sodium Na v channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling.

Introduction Animals use electrical signals to encode and propagate vital information, often over long distances Hille, Open in a separate window.

Figure 1. Gating mechanisms Voltage gating. Figure 2. Figure 3. Pore gating. Electromechanical coupling. Fast inactivation gating. Pharmacology Mechanisms of Na v channel pharmacology will be discussed as well as the possible roles of membrane-facing fenestrations, long predicted, and now recently visualized in Na v channel structures. Mechanisms of therapeutic inhibition by local anesthetics.

Toxins that target Na v channels. Figure 4. Brevetoxins and ciguatoxins. Cone snail toxins. Toxins influencing Na v channel gating by interacting with the VSDs. Scorpion toxins.

Spider toxins. Sea anemone toxins. Wasp toxins. Conclusion and future prospects Na v channels have played the role of biophysical muse for generations of membrane biophysicists.

Acknowledgments B. Ahern, F. Bosmans, and B. Chanda declare no competing financial interests. Richard W. Aldrich served as editor. References Abriel H. Regulation of the voltage-gated cardiac sodium channel Nav1. Trends Cardiovasc. Purification of the tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from Electrophorus electricus electroplax membranes.

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A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. Sodium current experiments. Mechanism of electromechanical coupling in voltage-gated potassium channels. Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel.

Targeting voltage sensors in sodium channels with spider toxins. Trends Pharmacol. FEBS Lett. Deconstructing voltage sensor function and pharmacology in sodium channels. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors.

Conotoxins and the posttranslational modification of secreted gene products. Life Sci. I 1 -superfamily conotoxins and prediction of single d -amino acid occurrence.

Novel conotoxins from Conus striatus and Conus kinoshitai selectively block TTX-resistant sodium channels. Unidirectional sodium and potassium fluxes through the sodium channel of squid giant axons. Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom. Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons.

Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin. Block of sodium conductance and gating current in squid giant axons poisoned with quaternary strychnine. Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation. Pathomechanisms in channelopathies of skeletal muscle and brain.

Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor. Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes.

Molecular properties of voltage-sensitive sodium channels. From ionic currents to molecular mechanisms: The structure and function of voltage-gated sodium channels. Voltage-gated sodium channels at structure, function and pathophysiology. Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore.

International Union of Pharmacology. Nomenclature and structure-function relationships of voltage-gated sodium channels. Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation. Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. A unique role for the S4 segment of domain 4 in the inactivation of sodium channels.

Charge substitution for a deep-pore residue reveals structural dynamics during BK channel gating. Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels.

Basic mechanisms of voltage-sensing. Handbook of Ion Channels. Zheng J. Perspectives on: Conformational coupling in ion channels: Thermodynamics of electromechanical coupling in voltage-gated ion channels.

The SCN1A variant database: a novel research and diagnostic tool. Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel. Design of a specific activator for skeletal muscle sodium channels uncovers channel architecture.

Gating at the selectivity filter in cyclic nucleotide-gated channels. Reconstituted voltage-sensitive sodium channel from Electrophorus electricus : chemical modifications that alter regulation of ion permeability. Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels.

Two types of scorpion toxin receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel. Isoform-specific and pan-channel partners regulate trafficking and plasma membrane stability; and alter sodium channel gating properties. The Na V 1. Contact us at letters time. The Hitchhiker's Guide to the Galaxy was published Oct.

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