PMID- 10414291
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 868
DP  - 1999 Apr 30
TI  - Molecular characterization of two members of the T-type calcium channel family.
PG  - 131-43
AB  - In this chapter we review our recent studies on the cloning of two novel cDNAs
      (alpha 1G and alpha 1H), and present electrophysiological evidence that they
      encode low voltage-activated, T-type calcium channels (CavT.1 and CavT.2,
      respectively). The nucleotide sequences of these T channels are very different
      from high voltage-activated Ca2+ channels, which explains why they were not
      cloned earlier using homology-based strategies. We used a bioinformatic approach,
      cloning the first fragment in silico. We then used this fragment to screen human 
      heart and rat brain lambda gt10 libraries, leading to the cloning of two
      full-length cDNAs derived from distinct genes (CACNA1G and CACNA1H). The deduced 
      amino acid sequences of the T channels (alpha 1G and alpha 1H) are also very
      different from previously cloned Ca2+ and Na+ channels; however, there are
      regions of structural similarity. For example, the T channels also contain four
      repeats, and within each repeat there are six putative membrane-spanning regions 
      and a pore loop. Expression of these cloned channels in either Xenopus oocytes or
      HEK-293 cells leads to the formation of typical T-type currents. As observed for 
      native T currents, these channels activate at potentials near the resting
      membrane potential, inactivate rapidly, deactivate slowly, and have a tiny
      single-channel conductance. The currents generated by alpha 1G and alpha 1H are
      nearly identical in terms of their voltage dependence and kinetics. We present
      preliminary evidence that nickel may serve as a valuable tool in discriminating
      between these subtypes.
FAU - Perez-Reyes, E
AU  - Perez-Reyes E
AD  - Department of Physiology, Loyola University Medical Center, Maywood, Ilinois
      60153, USA. eperez@luc.edu
FAU - Lee, J H
AU  - Lee JH
FAU - Cribbs, L L
AU  - Cribbs LL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Benzimidazoles)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Calcium Channels, T-Type)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 27B90X776A (Mibefradil)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Benzimidazoles/pharmacology
MH  - Brain/metabolism
MH  - Calcium Channel Blockers
MH  - Calcium Channels/chemistry/*genetics
MH  - Calcium Channels, T-Type
MH  - Cloning, Molecular
MH  - Electrophysiology
MH  - Humans
MH  - Ion Channel Gating
MH  - Kinetics
MH  - Mibefradil
MH  - Molecular Sequence Data
MH  - Myocardium/metabolism
MH  - Rats
MH  - Sequence Alignment
MH  - Tetrahydronaphthalenes/pharmacology
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
AID - 10.1111/j.1749-6632.1999.tb11283.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 1999 Apr 30;868:131-43. doi:
      10.1111/j.1749-6632.1999.tb11283.x.