Abstract
It has been shown that small interfering RNA (siRNA) partial knockdown of the α2δ1 dihydropyridine receptor subunits cause a significant increase in the rate of activation of the L-type Ca 2+ current in myotubes but have little or no effect on skeletal excitation-contraction coupling. This study used permanent siRNA knockdown of α2δ1 to address two important unaddressed questions. First, does the α2δ1 subunit contribute to the size and/or spacing of tetradic particles? Second, is the α2δ1 subunit important for excitation-coupled calcium entry? We found that the size and spacing of tetradic particles is unaffected by siRNA knockdown of α2δ1, indicating that the visible particle represents the α1s subunit. Strikingly, >97% knockdown of α2δ1 leads to a complete loss of excitation-coupled calcium entry during KCl depolarization and a more rapid decay of Ca2+ transients during bouts of repetitive electrical stimulation like those occurring during normal muscle activation in vivo. Thus, we conclude that the α2δ 1 dihydropyridine receptor subunit is physiologically necessary for sustaining Ca2+ transients in response to prolonged depolarization or repeated trains of action potentials.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3023-3034 |
| Number of pages | 12 |
| Journal | Biophysical Journal |
| Volume | 94 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2008 |
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ASJC Scopus subject areas
- Biophysics
Cite this
α2δ1 dihydropyridine receptor subunit is a critical element for excitation-coupled calcium entry but not for formation of tetrads in skeletal myotubes. / Gach, Marcin P.; Cherednichenko, Gennady; Haarmann, Claudia; Lopez, Jose R.; Beam, Kurt G.; Pessah, Isaac N; Franzini-Armstrong, Clara; Allen, Paul D.
In: Biophysical Journal, Vol. 94, No. 8, 15.04.2008, p. 3023-3034.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - α2δ1 dihydropyridine receptor subunit is a critical element for excitation-coupled calcium entry but not for formation of tetrads in skeletal myotubes
AU - Gach, Marcin P.
AU - Cherednichenko, Gennady
AU - Haarmann, Claudia
AU - Lopez, Jose R.
AU - Beam, Kurt G.
AU - Pessah, Isaac N
AU - Franzini-Armstrong, Clara
AU - Allen, Paul D.
PY - 2008/4/15
Y1 - 2008/4/15
N2 - It has been shown that small interfering RNA (siRNA) partial knockdown of the α2δ1 dihydropyridine receptor subunits cause a significant increase in the rate of activation of the L-type Ca 2+ current in myotubes but have little or no effect on skeletal excitation-contraction coupling. This study used permanent siRNA knockdown of α2δ1 to address two important unaddressed questions. First, does the α2δ1 subunit contribute to the size and/or spacing of tetradic particles? Second, is the α2δ1 subunit important for excitation-coupled calcium entry? We found that the size and spacing of tetradic particles is unaffected by siRNA knockdown of α2δ1, indicating that the visible particle represents the α1s subunit. Strikingly, >97% knockdown of α2δ1 leads to a complete loss of excitation-coupled calcium entry during KCl depolarization and a more rapid decay of Ca2+ transients during bouts of repetitive electrical stimulation like those occurring during normal muscle activation in vivo. Thus, we conclude that the α2δ 1 dihydropyridine receptor subunit is physiologically necessary for sustaining Ca2+ transients in response to prolonged depolarization or repeated trains of action potentials.
AB - It has been shown that small interfering RNA (siRNA) partial knockdown of the α2δ1 dihydropyridine receptor subunits cause a significant increase in the rate of activation of the L-type Ca 2+ current in myotubes but have little or no effect on skeletal excitation-contraction coupling. This study used permanent siRNA knockdown of α2δ1 to address two important unaddressed questions. First, does the α2δ1 subunit contribute to the size and/or spacing of tetradic particles? Second, is the α2δ1 subunit important for excitation-coupled calcium entry? We found that the size and spacing of tetradic particles is unaffected by siRNA knockdown of α2δ1, indicating that the visible particle represents the α1s subunit. Strikingly, >97% knockdown of α2δ1 leads to a complete loss of excitation-coupled calcium entry during KCl depolarization and a more rapid decay of Ca2+ transients during bouts of repetitive electrical stimulation like those occurring during normal muscle activation in vivo. Thus, we conclude that the α2δ 1 dihydropyridine receptor subunit is physiologically necessary for sustaining Ca2+ transients in response to prolonged depolarization or repeated trains of action potentials.
UR - http://www.scopus.com/inward/record.url?scp=43149102290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43149102290&partnerID=8YFLogxK
U2 - 10.1529/biophysj.107.118893
DO - 10.1529/biophysj.107.118893
M3 - Article
C2 - 18192372
AN - SCOPUS:43149102290
VL - 94
SP - 3023
EP - 3034
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 8
ER -