Graphical Abstract Current Molecular Pharmacology, 2015, Vol. 8, No. 2 i Graphical Abstract

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 110 Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets?

Jörg Striessnig*, Nadine J. Ortner and Alexandra Pinggera

Pharmacology and Toxicology, Institute of Pharmacy and Center of Molecular Biosciences, University of Innsbruck, Innsbruck, Austria

Nifedipine Compound 8

This review discusses novel insight into the pathophysiological role of L-type calcium channels and the role of existing (e.g. nifedipine) or new (compound 8) L-type channel blockers as potential therapeutics for new indications.

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 123 Voltage-gated Calcium Channels and Autism Spectrum Disorders

Alexandra F. Breitenkampa, Jan Matthesa and Stefan Herzig*a aDepartment of Pharmacology, University of Cologne, Cologne, Germany

α2 CACNA1A -CaV2.1 CACNA1B - CaV2.2 CACNA1C - Ca 1.2 CACNG1 - γ1 γ δ V CACNG2 - γ2 CACNA1D - Ca 1.3 Cavα1 V CACNG3 - γ3 CACNA1E - CaV2.3 CACNG4 - γ4 β CACNA1F - CaV1.4 CACNG5 - γ5 CACNB1 - β1 CACNA2D1 - α2δ1 CACNA1G - CaV3.1 CACNG6 - γ6 CACNB2 - β2 CACNA2D2 - α2δ2 CACNA1H - CaV3.2 CACNG7 - γ7 CACNB3 - β3 CACNA2D3 - α2δ3 CACNA1I - CaV3.3 CACNG8 - γ8 CACNA1S - Ca 1.1 CACNB4 - β4 CACNA2D4 - α2δ4 V

Many isoforms (highlighted) of the pore-forming and auxiliary subunit of the complex have been connected to Autism Spectrum Disorders by genetic approaches. ii Current Molecular Pharmacology, 2015, Vol. 8, No. 2 Graphical Abstract

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 133 Calcium Channel Mutations in Cardiac Arrhythmia Syndromes

Matthew J. Betzenhauser1, Geoffrey S. Pitt2 and Charles Antzelevitch3,*

1Experimental Cardiology Program, Masonic Medical Research Laboratory, Utica, NY; 2Departments of Medicine (Cardiology), Pharmacology and Cancer Biology, and Neurobiology, Duke University School of Medicine, Durham, NC; 3Lankenau Institute for Medical Research, Wynnewood, PA 19096

Mutations in the cardiac L-type calcium channel contribute to the manifestation of Long QT, Timothy, Short QT, Early Repolariza- tion and Brugada syndromes.

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 143

Voltage-Gated Cav1 Channels in Disorders of Vision and Hearing

Mei-ling A. Joiner and Amy Lee*

Departments of Molecular Physiology and Biophysics, Otolaryngology-Head and Neck Surgery, and Neurology, University of Iowa

Cav1.3 and Cav1.4 channel complexes of inner hair cells (IHC) and photoreceptor (PR) cells, respectively, share a number of biophysical properties and modulatory at ribbon synapses (r = ribbon, sv = synaptic vesicles).

Graphical Abstract Current Molecular Pharmacology, 2015, Vol. 8, No. 2 iii

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 149

Cav1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells

David H.F. Vandael§, Andrea Marcantoni and Emilio Carbone†

Department of Drug Science, Laboratory of Cellular and Molecular Neuroscience, N.I.S. Center, I - 10125 Torino, Italy

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 162 Emerging Alternative Functions for the Auxiliary Subunits of the Voltage-Gated Calcium Channels

Franz Hofmann1,*, Anouar Belkacemi2 and Veit Flockerzi2 1FOR 923, Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany; 2Experimentelle und Klinische Pharmakologie und Toxikologie, Medizinische Fakultät, Universität des Saarlandes, 66421 Homburg, Germany

iv Current Molecular Pharmacology, 2015, Vol. 8, No. 2 Graphical Abstract

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 169

The R-Domain: Identification of an N-terminal Region of the 2-1 Subunit Which is Necessary and Sufficient for its Effects on Cav2.2 Calcium Currents

Lele Song, Italo A. Espinoza-Fuenzalida, Sarah Etheridge, Owen T. Jones and Elizabeth M. Fitzgerald* *Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Manchester, M13 9PT, UK

Molecular and electrophysiological approaches were used to identify the minimal region of 2 - the R-domain - that imparts the primary functional effects of 2 on Cav2.2, the N-type calcium channel.

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 180 Inhibition of Voltage-Gated Calcium Channels by RGK Proteins

Zafir Buraei1* and Jian Yang2* 1Department of Biology, Pace University, New York, NY 10038, USA; 2Department of Biological Sciences, Columbia University, New York, NY 10027, USA

RGK proteins tonically inhibit Voltage-Gated Calcium Channels (VGCC) via multiple mechanisms that depend on their - and/or 1 subunit binding. However, the presence of the VGCC  subunit is required.

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 188 Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels

Manu Ben-Johny*, Ivy E. Dick*, David Yue, Wanjun Yang, John B. Issa, Lingjie Sang, Shin Rong Lee, Worawan B. Limpitikul, Jacqueline Niu, Po Wei Kang, Rahul Banerjee, Jennifer S. Babich, Ho Namkung, Jiangyu Li, Manning Zhang, Philemon S. Yang and Daniel N. Yue

Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, Center for Cell Dynamics, Johns Hopkins University School of Medicine Graphical Abstract Current Molecular Pharmacology, 2015, Vol. 8, No. 2 v

Current Molecular Pharmacology, 2015, Vol. 8, No. 2 206 Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging

Gaetano Santulli1,2,* and Andrew R. Marks1,2,3

1The Wu Center for Molecular Cardiology, 2Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia Uni- versity Medical Center, 3Department of Medicine, Columbia University, New York, NY

We present here a systematic and updated overview of the functional roles of the major intracellular calcium release channels, IP3Rs and RyRs, in human pathophysiology