This entry represents the alpha-1D subunits of the Voltage-dependent calcium channel, L-type (LVDCC), which allow cells to slowly inactivate voltage-gated Ca2+ influx to weak depolarisations [[cite:PUB00007839]]. This property allows them to participate in important physiological functions, such as tonic neurotransmitter release in cochlear inner hair cells [[cite:PUB00007840]]. In addition, these properties make them ideally suited to contribute to subthreshold Ca2+ signalling, for example in hippocampal pyramidal cells [[cite:PUB00007841]]. Mutations in this channel have been associated with autism spectrum disorders and epilepsy [[cite:PUB00100491]].
', 'llm': False, 'checked': False, 'updated': False}, {'text': 'Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins [[cite:PUB00036034]]. The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.
\r\n\r\nVoltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.
', 'llm': False, 'checked': False, 'updated': False}, {'text': 'L-type calcium channels are formed from alpha-1S, alpha-1C, alpha-1D, and alpha-1F subunits. They are widely distributed and are well characterised in the heart, smooth and skeletal muscle, and some neurons. Their primary functions are in both excitation-contraction and excitation-secretion coupling. In skeletal muscle, the L-type calcium channels act as a voltage sensor for excitation-contraction coupling, and in cardiac muscle, they provide a pathway for calcium influx. Mutations affecting L-type channel subunits result in three diseases: (1) muscular dystrophy, which is characterised by a lack of functional skeletal muscle; (2) hypokalaemic periodic paralysis, which is characterised by episodic attacks of skeletal muscle weakness; and (3) malignant hyperthermia, which is the main cause of death due to anaesthesia. 1,4-dihydropyridines act as antagonists of these channels [[cite:PUB00036043], [cite:PUB00071805]].
', 'llm': False, 'checked': False, 'updated': False}, {'text': 'The alpha-1 subunit forms the pore for the import of extracellular calcium ions and, though regulated by the other subunits, is primarily responsible for the pharmacological properties of the channel [[cite:PUB00036040]]. It shares sequence characteristics with all voltage-dependent cation channels, and exploits the same 6-helix bundle structural motif -in both sodium and calcium channels, this motif is repeated 4 times within the sequence to give a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM) segments (S1, S2, S3, S5, S6) are hydrophobic, while the other (S4) is positively charged and serves as the voltage-sensor. Several genes encoding alpha-1 subunits have been identified and can be divided into three functionally distinct families based on sequence homology -Cav1, Cav2 and Cav3 [[cite:PUB00036041]]. The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium currents, while the Cav3 family mediates T-type calcium currents.
', 'llm': False, 'checked': False, 'updated': False}]" "" "[{'identifier': 'GO:0005245', 'name': 'voltage-gated calcium channel activity', 'category': {'code': 'F', 'name': 'molecular_function'}}, {'identifier': 'GO:0070588', 'name': 'calcium ion transmembrane transport', 'category': {'code': 'P', 'name': 'biological_process'}}, {'identifier': 'GO:0005891', 'name': 'voltage-gated calcium channel complex', 'category': {'code': 'C', 'name': 'cellular_component'}}]" "{'accession': 'IPR002077', 'name': 'Voltage-dependent calcium channel, alpha-1 subunit', 'type': 'Family', 'children': [{'accession': 'IPR005446', 'name': 'Voltage-dependent calcium channel, L-type, alpha-1 subunit', 'type': 'Family', 'children': [{'accession': 'IPR005450', 'name': 'Voltage-dependent calcium channel, L-type, alpha-1S subunit', 'type': 'Family', 'children': []}, {'accession': 'IPR005451', 'name': 'Voltage-dependent calcium channel, L-type, alpha-1C subunit', 'type': 'Family', 'children': []}, {'accession': 'IPR005452', 'name': 'Voltage-dependent calcium channel, L-type, alpha-1D subunit', 'type': 'Family', 'children': []}]}, {'accession': 'IPR005447', 'name': 'Voltage-dependent calcium channel, N-type, alpha-1 subunit', 'type': 'Family', 'children': []}, {'accession': 'IPR005448', 'name': 'Voltage-dependent calcium channel, P/Q-type, alpha-1 A', 'type': 'Family', 'children': []}, {'accession': 'IPR005449', 'name': 'Voltage-dependent calcium channel, R-type, alpha-1 subunit', 'type': 'Family', 'children': []}]}" "" False False False "{'PUB00071805': {'PMID': 15336981, 'ISBN': None, 'volume': '322', 'issue': '4', 'year': 2004, 'title': 'L-type Ca2+ channels in Ca2+ channelopathies.', 'URL': None, 'raw_pages': '1341-6', 'medline_journal': 'Biochem Biophys Res Commun', 'ISO_journal': 'Biochem. Biophys. Res. Commun.', 'authors': ['Striessnig J', 'Hoda JC', 'Koschak A', 'Zaghetto F', 'Mullner C', 'Sinnegger-Brauns MJ', 'Wild C', 'Watschinger K', 'Trockenbacher A', 'Pelster G.'], 'DOI_URL': 'http://dx.doi.org/10.1016/j.bbrc.2004.08.039'}, 'PUB00007839': {'PMID': 11285265, 'ISBN': None, 'volume': '276', 'issue': '25', 'year': 2001, 'title': 'alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages.', 'URL': None, 'raw_pages': '22100-6', 'medline_journal': 'J Biol Chem', 'ISO_journal': 'J. Biol. Chem.', 'authors': ['Koschak A', 'Reimer D', 'Huber I', 'Grabner M', 'Glossmann H', 'Engel J', 'Striessnig J.'], 'DOI_URL': 'http://dx.doi.org/10.1074/jbc.M101469200'}, 'PUB00036043': {'PMID': 12825828, 'ISBN': None, 'volume': '23', 'issue': '3', 'year': 2003, 'title': '1,4-Dihydropyridines as calcium channel ligands and privileged structures.', 'URL': None, 'raw_pages': '293-303', 'medline_journal': 'Cell Mol Neurobiol', 'ISO_journal': 'Cell. Mol. Neurobiol.', 'authors': ['Triggle DJ.'], 'DOI_URL': 'http://dx.doi.org/10.1023/A:1023632419813'}, 'PUB00036040': {'PMID': 11031246, 'ISBN': None, 'volume': '16', 'issue': None, 'year': 2000, 'title': 'Structure and regulation of voltage-gated Ca2+ channels.', 'URL': None, 'raw_pages': '521-55', 'medline_journal': 'Annu Rev Cell Dev Biol', 'ISO_journal': 'Annu. Rev. Cell Dev. Biol.', 'authors': ['Catterall WA.'], 'DOI_URL': 'http://dx.doi.org/10.1146/annurev.cellbio.16.1.521'}, 'PUB00036041': {'PMID': 10774722, 'ISBN': None, 'volume': '25', 'issue': '3', 'year': 2000, 'title': 'Nomenclature of voltage-gated calcium channels.', 'URL': None, 'raw_pages': '533-5', 'medline_journal': 'Neuron', 'ISO_journal': 'Neuron', 'authors': ['Ertel EA', 'Campbell KP', 'Harpold MM', 'Hofmann F', 'Mori Y', 'Perez-Reyes E', 'Schwartz A', 'Snutch TP', 'Tanabe T', 'Birnbaumer L', 'Tsien RW', 'Catterall WA.'], 'DOI_URL': 'http://dx.doi.org/10.1016/S0896-6273(00)81057-0'}, 'PUB00036034': {'PMID': 14657414, 'ISBN': None, 'volume': '55', 'issue': '4', 'year': 2003, 'title': 'International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels.', 'URL': None, 'raw_pages': '579-81', 'medline_journal': 'Pharmacol Rev', 'ISO_journal': 'Pharmacol. Rev.', 'authors': ['Catterall WA', 'Striessnig J', 'Snutch TP', 'Perez-Reyes E; International Union of Pharmacology.'], 'DOI_URL': 'http://dx.doi.org/10.1124/pr.55.4.8'}, 'PUB00007841': {'PMID': 8930286, 'ISBN': None, 'volume': '76', 'issue': '5', 'year': 1996, 'title': 'Dihydropyridine-sensitive, voltage-gated Ca2+ channels contribute to the resting intracellular Ca2+ concentration of hippocampal CA1 pyramidal neurons.', 'URL': None, 'raw_pages': '3460-70', 'medline_journal': 'J Neurophysiol', 'ISO_journal': 'J. Neurophysiol.', 'authors': ['Magee JC', 'Avery RB', 'Christie BR', 'Johnston D.'], 'DOI_URL': 'http://intl-jn.physiology.org/cgi/content/abstract/76/5/3460'}, 'PUB00007840': {'PMID': 10639174, 'ISBN': None, 'volume': '97', 'issue': '2', 'year': 2000, 'title': 'Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse.', 'URL': None, 'raw_pages': '883-8', 'medline_journal': 'Proc Natl Acad Sci U S A', 'ISO_journal': 'Proc. Natl. Acad. Sci. U.S.A.', 'authors': ['Moser T', 'Beutner D.'], 'DOI_URL': 'http://dx.doi.org/10.1073/pnas.97.2.883'}, 'PUB00100491': {'PMID': 28472301, 'ISBN': None, 'volume': '26', 'issue': '15', 'year': 2017, 'title': 'New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy.', 'URL': None, 'raw_pages': '2923-2932', 'medline_journal': 'Hum Mol Genet', 'ISO_journal': 'Hum Mol Genet', 'authors': ['Pinggera A', 'Mackenroth L', 'Rump A', 'Schallner J', 'Beleggia F', 'Wollnik B', 'Striessnig J.'], 'DOI_URL': None}}" "{'prints': {'PR01636': 'LVDCCALPHA1D'}}" "{'name': 'Voltage-dependent calcium channel, L-type, alpha-1D subunit', 'short': 'LVDCC_a1dsu'}" "[{'accession': 'IPR027359', 'name': 'Voltage-dependent channel domain superfamily', 'type': 'homologous_superfamily'}]" "" "" "interpro" "family" ""