Regulation of the cardiac L-type calcium channel in L6 cells by arginine-vasopressin

TY - JOUR

T1 - Regulation of the cardiac L-type calcium channel in L6 cells by arginine-vasopressin

AU - Hantash, Basil M.

AU - Thomas, Andrew P.

AU - Reeves, John P.

PY - 2006/12/15

Y1 - 2006/12/15

N2 - L-type Ca2+ channel activity was measured in L6 cells as nifedipine-sensitive barium (Ba2+; 5 mM) influx in a depolarizing salt solution containing 140 mM KCl. Addition of AVP (arginine-vasopressin) during Ba2+ uptake reduced the rate of Ba2+ influx by 60-100%; this was followed by a gradual restoration of the initial rate of Ba2+ uptake. Blockade of PKC (protein kinase C) by pretreatment with 10 μM bisindolylmaleimide did not affect the initial inhibition of Ba 2+ influx, but completely abolished the recovery phase. The effect of AVP was half-maximal at 10 nM AVP and was blocked by the Via receptor antagonist d-(CH2)5-Tyr(Me)-AVP. Activation of G αs by isoprenaline or cholera toxin antagonized the actions of AVP on Ba2+ uptake. This protection persisted in the presence of the PKA (protein kinase A) inhibitor KT5720, and was not mimicked by agents that increase cAMP. Inhibition of Ba2+ influx was also elicited by ATP and ET (endothelin 1) with an order of effectiveness ET < ATP < AVP. Each of these agents has been reported to act through Gq-coupled receptors. We conclude that activation of Gq-coupled receptors produces a rapid inhibition of the cardiac L-type Ca2+ channel, which is subsequently overcome by activation of PKC.

AB - L-type Ca2+ channel activity was measured in L6 cells as nifedipine-sensitive barium (Ba2+; 5 mM) influx in a depolarizing salt solution containing 140 mM KCl. Addition of AVP (arginine-vasopressin) during Ba2+ uptake reduced the rate of Ba2+ influx by 60-100%; this was followed by a gradual restoration of the initial rate of Ba2+ uptake. Blockade of PKC (protein kinase C) by pretreatment with 10 μM bisindolylmaleimide did not affect the initial inhibition of Ba 2+ influx, but completely abolished the recovery phase. The effect of AVP was half-maximal at 10 nM AVP and was blocked by the Via receptor antagonist d-(CH2)5-Tyr(Me)-AVP. Activation of G αs by isoprenaline or cholera toxin antagonized the actions of AVP on Ba2+ uptake. This protection persisted in the presence of the PKA (protein kinase A) inhibitor KT5720, and was not mimicked by agents that increase cAMP. Inhibition of Ba2+ influx was also elicited by ATP and ET (endothelin 1) with an order of effectiveness ET < ATP < AVP. Each of these agents has been reported to act through Gq-coupled receptors. We conclude that activation of Gq-coupled receptors produces a rapid inhibition of the cardiac L-type Ca2+ channel, which is subsequently overcome by activation of PKC.

KW - Arginine-vasopressin (AVP)

KW - Cardiac L-type calcium channel

KW - G-protein

KW - L6 cell

KW - Protein kinase C (PKC)

UR - http://www.scopus.com/inward/record.url?scp=33845799661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845799661&partnerID=8YFLogxK

U2 - https://doi.org/10.1042/BJ20060742

DO - https://doi.org/10.1042/BJ20060742

M3 - Article

C2 - 16913857

VL - 400

SP - 411

EP - 419

JO - The Biochemical journal

JF - The Biochemical journal

SN - 0264-6021

IS - 3

ER -