Evolutionary insights into T-type Ca2+channel structure, function, and ion selectivity from theTrichoplax adhaerenshomologue.
Four-domain voltage-gated Ca2+(Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cavchannels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells. Here, we characterize the single T-type calcium channel fromTrichoplax adhaerens(TCav3), an early diverging animal that lacks muscle, neurons, and synapses. Co-immunolocalization using antibodies against TCav3 and neurosecretory cell marker complexin labeled gland cells, which are hypothesized to play roles in paracrine signaling. Cloning and in vitro expression of TCav3 reveals that, despite roughly 600 million years of divergence from other T-type channels, it bears the defining structural and biophysical features of the Cav3 family. We also characterize the channel's cation permeation properties and find that its pore is less selective for Ca2+over Na+compared with the human homologue Cav3.1, yet it exhibits a similar potent block of inward Na+current by low external Ca2+concentrations (i.e., the Ca2+block effect). A comparison of the permeability features of TCav3 with other cloned channels suggests that Ca2+block is a locus of evolutionary change in T-type channel cation permeation properties and that mammalian channels distinguish themselves from invertebrate ones by bearing both stronger Ca2+block and higher Ca2+selectivity. TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure-function properties, ion selectivity, and cellular physiology.
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
Carolyn L
CL
Smith
University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.
Salsabil
S
Abdallah
University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.
Yuen Yan
http://orcid.org/0000-0002-9567-5304
YY
Wong
University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.
Phuong
P
Le
University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.
Alicia N
AN
Harracksingh
Georgia State University, Atlanta, GA 30302.
Liana
L
Artinian
Georgia State University, Atlanta, GA 30302.
Arianna N
AN
Tamvacakis
Georgia State University, Atlanta, GA 30302.
Vincent
V
Rehder
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
Thomas S
TS
Reese
University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada adriano.senatore@utoronto.ca.
Adriano
http://orcid.org/0000-0001-5180-1180
A
Senatore
D000818:Animals; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D010802:Phylogeny; D054909:Placozoa / Q000737:chemistry / Q000378:metabolism
D020747:Calcium Channels, T-Type