Charade of the SR K+-channel: two ion-channels, TRIC-A and TRIC-B, masquerade as a single K+-channel.
The presence of a sarcoplasmic reticulum (SR) K+-selective ion-channel has been known for >30 years yet the molecular identity of this channel has remained a mystery. Recently, an SR trimeric intracellular cation channel (TRIC-A) was identified but it did not exhibit all expected characteristics of the SR K+-channel. We show that a related SR protein, TRIC-B, also behaves as a cation-selective ion-channel. Comparison of the single-channel properties of purified TRIC-A and TRIC-B in symmetrical 210 mM K+ solutions, show that TRIC-B has a single-channel conductance of 138 pS with subconductance levels of 59 and 35 pS, whereas TRIC-A exhibits full- and subconductance open states of 192 and 129 pS respectively. We suggest that the K+-current fluctuations observed after incorporating cardiac or skeletal SR into bilayers, can be explained by the gating of both TRIC-A and TRIC-B channels suggesting that the SR K+-channel is not a single, distinct entity. Importantly, TRIC-A is regulated strongly by trans-membrane voltage whereas TRIC-B is activated primarily by micromolar cytosolic Ca2+ and inhibited by luminal Ca2+. Thus, TRIC-A and TRIC-B channels are regulated by different mechanisms, thereby providing maximum flexibility and scope for facilitating monovalent cation flux across the SR membrane.
Pitt
Samantha J
SJ
Department of Physiology and Pharmacology and Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.
Park
Ki-Ho
KH
Nishi
Miyuki
M
Urashima
Toshiki
T
Aoki
Sae
S
Yamazaki
Daijyu
D
Ma
Jianjie
J
Takeshima
Hiroshi
H
Sitsapesan
Rebecca
R
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000302:isolation & purification / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep
D015221:Potassium Channels; D011189:Potassium Chloride; D002118:Calcium