Front. Pharmacol.Frontiers in PharmacologyFront. Pharmacol.1663-9812Frontiers Media S.A.10.3389/fphar.2017.00112PharmacologyCorrectionCorrigendum: Sustained Contraction in Vascular Smooth Muscle by Activation of L-type Ca2+ Channels Does Not Involve Ca2+ Sensitization or CaldesmonEtsHillevi K.1SeowChun Y.2*MorelandRobert S.13†1Department of Pharmacology and Physiology, Drexel University College of MedicinePhiladelphia, PA, USA2Department of Pathology and Laboratory Medicine, University of British ColumbiaVancouver, BC, Canada3Department of Pathology and Laboratory Medicine, Drexel University College of MedicinePhiladelphia, PA, USA
Edited by: Issy Laher, University of British Columbia, Canada
Reviewed by: Issy Laher, University of British Columbia, Canada; Philip Aaronson, King's College London, UK; Chris Rembold, University of Virginia, USA; Michael A. Hill, University of Missouri, USA
*Correspondence: Chun Y. Seow chun.seow@hli.ubc.ca
This article was submitted to Cardiovascular and Smooth Muscle Pharmacology, a section of the journal Frontiers in Pharmacology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
A corrigendum on Sustained Contraction in Vascular Smooth Muscle by Activation of L-type Ca2+ Channels Does Not Involve Ca2+ Sensitization or Caldesmon by Ets, H. K., and Seow, C.Y. (2016). Front. Pharmacol. 7:516. doi: 10.3389/fphar.2016.00516carotid arteryBay K8644nifedipinemyosin light chain kinaseprotein kinase CMAP kinaseRho kinase
Results from our recent publication indicate that sustained contraction in vascular smooth muscle induced by Bay K8644 is independent from Rho-kinase (ROCK) associated calcium sensitization. We have failed to recognize and properly acknowledge an earlier study by Alvarez et al. (2010) that reached the same conclusion. In their study Alvarez et al. clearly demonstrated that phosphorylation of MYPT1, a downstream substrate of ROCK, was not increased by Bay K8644 activation and therefore the calcium-dependent myosin light chain (MLC) phosphorylation and the associated sustained tension maintenance cannot be the consequence of Bay K8644-induced MYPT1 phosphorylation. In our study Bay K8644 also failed to increase MYPT1 phosphorylation, and in addition we found that phosphorylation of CPI-17, a downstream substrate for PKC and ROCK, was not changed by Bay K8644 activation either. Taken together, results from both studies strongly suggest that an increase in intracellular calcium concentration in vascular smooth muscle does not necessarily lead to activation of ROCK and the associated calcium sensitization.
The concept of calcium sensitization in smooth muscle activation was first described by Morgan and Morgan (1984). In vascular smooth muscle they found that agonist (phenylephrine) stimulation, compared with the stimulation by potassium depolarization, led to more force generation at lower intracellular calcium concentrations. Rembold and Murphy (1988) also observed a stronger calcium-sensitizing effect of agonist stimulation relative to potassium depolarization. Furthermore they revealed that the sensitization step occurred in between the release of calcium and MLC phosphorylation, and not between MLC phosphorylation and force generation.
The lack of calcium-sensitizing effect of Bay K8644 has also been recognized by Rembold (1990). An important revelation of the study is that calcium sensitization is linked to stimulation of G proteins, and potassium depolarization and Bay K8644 are poor activators of G protein-coupled receptors, at least in vascular smooth muscle.
Although our report is not meant to be a review, we regret that the above cited studies were not included. We believe that addition of these references will provide our readers with a more complete history in the search for mechanisms underlying calcium sensitization.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
ReferencesAlvarezS. M.MinerA. S.BrowneB. M.RatzP. H. (2010). Failure of Bay K 8644 to induce RhoA kinase-dependent calcium sensitization in rabbit blood vessels. Br. J. Pharmacol.160, 1326–1337. 10.1111/j.1476-5381.2010.00751.x20590624MorganJ. P.MorganK. G. (1984). Stimulus-specific patterns of intracellular calcium levels in smooth muscle of ferret portal vein. J. Physiol.351, 155–167. 10.1113/jphysiol.1984.sp0152396747864RemboldC. M. (1990). Modulation of the [Ca2+] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J. Physiol.429, 77–94. 10.1113/jphysiol.1990.sp0182451703575RemboldC. M.MurphyR. A. (1988). Myoplasmic [Ca2+] determines myosin phosphorylation in agonist-stimulated swine arterial smooth muscle. Circ. Res.63, 593–603. 10.1161/01.RES.63.3.5933409490