The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution.

Abstract

Glutamate release from rod photoreceptors is dependent on a sustained calcium influx through L-type calcium channels. Missense mutations in the CACNA1F gene in patients with incomplete X-linked congenital stationary night blindness implicate the Ca(v)1.4 calcium channel subtype. Here, we describe the functional and pharmacological properties of transiently expressed human Ca(v)1.4 calcium channels. Ca(v)1.4 is shown to encode a dihydropyridine-sensitive calcium channel with unusually slow inactivation kinetics that are not affected by either calcium ions or by coexpression of ancillary calcium channel beta subunits. Additionally, the channel supports a large window current and activates near -40 mV in 2 mM external calcium, making Ca(v)1.4 ideally suited for tonic calcium influx at typical photoreceptor resting potentials. Introduction of base pair changes associated with four incomplete X-linked congenital night blindness mutations showed that only the G369D alteration affected channel activation properties. Immunohistochemical analyses show that, in contrast with previous reports, Ca(v)1.4 is widely distributed outside the retina, including in the immune system, thus suggesting a broader role in human physiology.

• Authors: John E McRory, Jawed Hamid, Clinton J Doering, Esperanza Garcia, Robin Parker, Kevin Hamming, Lina Chen, Michael Hildebrand, Aaron M Beedle, Laura Feldcamp, Gerald W Zamponi, Terrance P Snutch
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 24 Issue 7 Pg. 1707-18 (Feb 18 2004) ISSN: 1529-2401 [Electronic] United States
• PMID: 14973233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CACNA1F protein, human
• Calcium Channels
• Calcium Channels, L-Type
• RNA, Messenger

Topics

• Adrenal Glands (metabolism)
• Amino Acid Substitution
• Animals
• Bone Marrow (metabolism)
• Calcium Channels (genetics, metabolism)
• Calcium Channels, L-Type (genetics, metabolism)
• Cell Line
• Genetic Diseases, X-Linked (genetics)
• Humans
• Kidney (cytology, metabolism)
• Mast Cells (metabolism)
• Muscles (metabolism)
• Mutation
• Night Blindness (genetics)
• Organ Specificity
• Patch-Clamp Techniques
• Plasma Cells (metabolism)
• RNA, Messenger (biosynthesis)
• Rats
• Retina (metabolism)
• Spinal Cord (metabolism)
• Spleen (metabolism)