AG Schubert
Projekte
In der Forschung werden folgende Schwerpunkte verfolgt:
Untersuchung der
- Vielfalt der Funktionen von Ionenkanälen, insbesondere von Kaliumkanälen, im Kreislaufsystem verschiedener Organe (organotypische Bestimmung)
- der Plastizität der arteriellen Kontraktilitätsmechanismen unter physiologischen (postnatales Remodeling) und pathophysiologischen (Diabetes) Bedingungen und die Regulation dieser Prozesse
Regulation and function of vascular smooth muscle potassium channels
We have shown that BK channels are regulated by a number of signalling pathways, by PKG (Robertson et al., 1993;Gribkova et al., 2002;Gagov et al., 2022), by PKA (Schubert et al., 1996) – also in hypertension (Pyanova et al., 2024), by PKC (Schubert et al., 1999b;Mladenov et al., 2008) as well as intracellular pH (Petkova-Kirova et al., 2000;Schubert et al., 2001). In small arteries, these signalling pathways mediate the contribution of BK channels to NO- and iloprost-induced dilations (Climent et al. 2012;Iozzi et al. 2013;Sausbier et al., 2000;Sausbier et al., 2005;Schubert et al., 1997), to ghrelin- (Mladenov et al., 2008) and methoxamine-induced vasocontraction, where the latter was shown to increase with postnatal maturation (Mladenov et al., 2008; Shvetsova et al., 2019, Ma et al., 2020) as well as to the setting of the level of the myogenic tone (Wesselman et al., 1997;Schubert et al., 1999a; Ma et al., 2020). Interestingly, when the full range of vessel tone was explored, NO-induced dilations were shown to be limited by BK channels, only at high levels of vessel tone BK channels facilitate this dilation (Schmid et al., 2018). All these findings were obtained on different small arteries from rats and PKG- as well as BK channel-deficient mice. Some of these data have been summarized in a review article (Schubert & Nelson, 2001).
Further, we could demonstrate that inwardly rectifying potassium (Kir2) channels are activated by NO, where this effect contributes to the NO-induced dilation of small arteries (Schubert et al., 2004) and that the negative feedback regulation of vasocontraction by Kir2 channels decreases during postnatal maturation (Shvetsova et al., 2019).
Ongoing studies are focused on the biophysical and pharmacological properties of several voltage-operated potassium channels and their function in the cardiovascular system. It was found that Kv7 channels contribute to the vasodilating effect of factors released from periadventitial fat (Schleifenbaum et al. 2010; Zavaritskaya et al. 2013, Tsvetkov et al 2016), as well as CO (Zhang et al. 2021), lose their dominating role in the negative feedback regulation of vasocontraction during postnatal maturation (Shvetsova et al., 2019; Ma et al., 2020) and are limited in their role as negative feedback on vasoconstriction by BK channels (Ma et al., 2020). These channels share with BK channels the ability to mediate vasodilation by the novel K channels opener GoSlo (Zavaritskaya et al. 2020). Another Kv channel, Kv2.1, was identified to prevent vasomotion and safeguard myogenic reactivity (Här et al., 2023). Recently, it was shown that another class of K channels, TASK-1 channels, also lose their ability to mediate negative feedback on vasocontraction during postnatal maturation (Shvetsova et al., 2020) and are involved in pH-dependent tone regulation in renal arteries (Shvetsova et al., 2022).
Overviews of the tools to study Kv7 channels and of the role of different K channels in early postnatal maturation have been presented in reviews (Gollasch et al., 2018; Svetsova et al., 2021; Schubert et al., 2023).
Climent, B., Schubert, R., Stankevicius, E., Garcia-Sacristan, A., Simonsen, U., Rivera, L. (2012). Large conductance Ca2+-activated K+ channels modulate endothelial cell outward currents and nitric oxide release in the intact rat superior mesenteric artery. BBRC 417, 1007-1013.
Gollasch,M., Welsh,D.G., Schubert,R. (2018). Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension. Microcirculation. 25: e12434
Gribkova, I. V., Schubert, R., & Serebriakov, V. N. (2002). [Study of NO action on calcium-activated potassium channel of the rat artery smooth muscle cells]. Ross.Fiziol.Zh.Im I.M.Sechenova 88, 1199-1205.
Iozzi, D., Schubert, R., Kalenchuk, V.U., Neri, A., Sgaragli, G., Fusi, F., Saponara, S. (2013). Quercetin relaxes rat tail main artery partly via a PKG-mediated stimulation of KCa1.1 channels. Acta Physiol. 208, 329-39.
Ma,D., Gaynullina,D.K., Schmidt,N., Mladenov,M., Schubert,R. (2020). The functional availability of arterial Kv7 channels is suppressed considerably by large-conductance calcium-activated potassium channels in 2- to 3-month old but not in 10- to 15-day old rats. Front Physiol 11: 597395
Mladenov, M. I., Hristov, K. L., Dimitriova, D. Z., Schubert, R., Lubomirov, L. T., Gjorgoski, I. K., Duridanova, D. B., Gagov, H. S. (2008). Ghrelin signalling in guinea-pig femoral artery smooth muscle cells. Acta Physiol (Oxf) 194, 195-206.
Petkova-Kirova, P., Gagov, H., Krien, U., Duridanova, D., Noack, T., Schubert, R. (2000). 4-aminopyridine affects rat arterial smooth muscle BK(Ca) currents by changing intracellular pH. Br.J.Pharmacol. 131, 1643-1650.
Robertson, B. E., Schubert, R., Hescheler, J., Nelson, M. T. (1993). cGMP-Dependent Protein Kinase Activates Ca-Activated K- Channels in Cerebral Artery Smooth Muscle Cells. Am.J.Physiol. 265, C299-C303.
Sausbier, M., Arntz, C., Bucurenciu, I., Zhao, H., Zhou, X. B., Sausbier, U., Feil, S., Kamm, S., Essin, K., Sailer, C. A., Abdullah, U., Krippeit-Drews, P., Feil, R., Hofmann, F., Knaus, H. G., Kenyon, C., Shipston, M. J., Storm, J. F., Neuhuber, W., Korth, M., Schubert, R., Gollasch, M., Ruth, P. (2005). Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. Circulation 112, 60-68.
Sausbier, M., Schubert, R., Voigt, V., Hirneiss, C., Pfeifer, A., Korth, M., Kleppisch, T., Ruth, P., Hofmann, F. (2000). Mechanisms of NO/cGMP-dependent vasorelaxation. Circ.Res. 87, 825-830.
Schleifenbaum, J., Köhn, C., Voblova, N., Dubrovska, G., Zavarirskaya, O., Gloe, T., Crean, C.S., Luft, F.C., Huang, Y., Schubert, R., Gollasch, M. (2010). Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 28, 1875-82.
Schmid,J., Müller,B., Heppeler,D., Gaynullina,D., Kassmann,M., Gagov,H., Mladenov,M., Gollasch,M., Schubert,R. (2018). The Unexpected Role of Calcium-Activated Potassium Channels: Limitation of NO-Induced Arterial Relaxation. J Am Heart Assoc. 7: e007808
Schubert, R., Krien, U., Gagov, H. (2001). Protons inhibit the BK(Ca) channel of rat small artery smooth muscle cells. J.Vasc.Res. 38, 30-38.
Schubert, R., Krien, U., Wulfsen, I., Schiemann, D., Lehmann, G., Ulfig, N., Veh, R. W., Schwarz, J. R., Gagov, H. (2004). Nitric oxide donor sodium nitroprusside dilates rat small arteries by activation of inward rectifier potassium channels. Hypertension 43, 891-896.
Schubert, R., Lehmann, G., Serebryakov, V. N., Mewes, H., Hopp, H.-H. (1999a). cAMP-dependent protein kinase is in an active state in rat small arteries possessing a myogenic tone. Am.J.Physiol. 277, H1145-H1155.
Schubert, R. Nelson, M. T. (2001). Protein kinases: tuners of the BKCa channel in smooth muscle. Trends Pharmacol.Sci. 22, 505-512.
Schubert, R., Noack, T., Serebryakov, V. N. (1999b). Protein kinase C reduces the KCa current of rat tail artery smooth muscle cells. Am.J.Physiol. 276, C648-C658.
Schubert, R., Serebryakov, V. N., Engel, H., Hopp, H.-H. (1996). Iloprost activates KCa channels of vascular smooth muscle cells: role of cAMP-dependent protein kinase. Am.J.Physiol. 271, C1203-C1211.
Schubert, R., Serebryakov, V. N., Mewes, H., Hopp, H.-H. (1997). Iloprost dilates rat small arteries: role of KATP- and KCa-channel activation by cAMP-dependent protein kinase. Am.J.Physiol. 272, H1147-H1156.
Shvetsova,A.A., Gaynullina,D.K., Tarasova,O.S., Schubert,R. (2019). Negative feedback regulation of vasocontraction by potassium channels in 10-to 15-day-old rats: Dominating role of K(v)7 channels Acta Physiol 225: e13176
Shvetsova,A., Gaynullina,D.K., Schmidt,N., Bugert,P., Lukoshkova,E.V., Tarasova,O.S., Schubert,R. (2020). TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1‐ to 2‐week‐old but not adult rats. Br. J. Pharmacol. 177:c5148-5162
Shvetsova,A.A., Gaynullina,D.K., Tarasova,O.S., Schubert,R. (2021). Remodeling of arterial tone regulation in postnatal development: focus on smooth muscle cell potassium channels. International Journal of Molecular Sciences 22: 5413
Tsvetkov, D., Tano, J.Y., Kassmann, M., Wang, N., Schubert, R., Gollasch, M. (2016). The Role of DPO-1 and XE991-Sensitive Potassium Channels in Perivascular Adipose Tissue-Mediated Regulation of Vascular Tone. Front Physiol. 7, 335
Wesselman, J. P. M., Schubert, R., VanBavel, E., Nilsson, H., Mulvany, M. J. (1997). KCa-channel blockade prevents sustained pressure-induced depolarization in rat mesenteric small arteries. Am.J.Physiol. 272, H2241-H2249.
Zavaritskaya, O., Zhuravleva, N., Schleifenbaum, J., Gloe, T., Devermann, L., Kluge, R., Mladenov, M., Frey, M., Gagov, H., Fésüs, G., Gollasch, M., Schubert, R. (2013). Role of KCNQ Channels in Skeletal Muscle Arteries and Periadventitial Vascular Dysfunction. Hypertension 61, 151-59.
Zavaritskaya,O., Dudem,S., Ma,D., Rabab,K.E., Albrecht,S., Tsvetkov,D., Kassmann,M., Thornbury,K., Mladenov,M., Kammermeier,C., Sergeant,G., Mullins,N., Wouappi,O., Wurm,H., Kannt,A., Gollasch,M., Hollywood,M.A., Schubert,R. (2020). Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and Kv7 channels. Br. J. Pharmacol. 177: 1164-1186
Zhang,D., Krause,B.M., Schmalz,H.G., Wohlfart,P., Yard,B.A., Schubert,R. (2021). ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels. Front Pharmacol. 6, 702392
Shvetsova,A.A., Lazarenko,V.S., Gaynullina,D.K., Tarasova,O.S., Schubert,R. (2022) TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline pH. Front. Physiol. 13:895863.
Gagov,H., Gribkova,I.V., Serebryakov,V.N., Schubert,R. (2022) Sodium Nitroprusside-Induced Activation of Vascular Smooth Muscle BK Channels Is Mediated by PKG Rather Than by a Direct Interaction with NO. International Journal of Molecular Sciences 23: 2798
Här,K., Lysenko,N.N., Dimitrova,D., Schlüter,T., Zavaritskaya,O., Kamkin,A.G., Mladenov,M., Grisk,O., Köhler,R., Gagov,H., Schubert,R. (2023) Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries. Cells 12: 1989
Schubert,R., Gaynullina,D.K., Shvetsova,A.A., Tarasova,O.S. (2023) Myography of isolated blood vessels: Considerations for experimental design and combination with supplementary
techniques. Front. Physiol. 14: 1176748.
Pyanova,A., Serebryakov,V.N., Gagov,H., Mladenov,M., Schubert,R. (2024) BK Channels in Tail Artery Vascular Smooth Muscle Cells of Normotensive (WKY) and Hypertensive (SHR) Rats Possess Similar Calcium Sensitivity but Different Responses to the Vasodilator Iloprost. International Journal of Molecular Sciences 25: 7140
Functional remodeling of vascular smooth muscle during early postnatal development
Our studies showed that the signaling mechanisms governing vascular tone regulation possess a high degree of plasticity. Thus, with postnatal maturation (i) the anticontractile effect of the endothelium decreases (Gaynullina et al. 2013), (ii) sympathetic nerves reduce arterial smooth muscle Ca2+-sensitivity (Puzdrova et al. 2014), (iii) mRNA and miRNA expression changes in a correlated manner (Gaynullina et al. 2015), (iv) Rho-kinase-mediated calcium sensitivity decreases (Mochalov et al., 2018), (v) Kv1, Kv7 and Kir2-channel mediated negative feedback of vasocontraction is reduced, in the case of Kv7 channel in part due to an increasing role of BK channels (Shvetsova et al., 2019; Ma et al. 2020), and (vi) the TASK-1 channel mediated negative feedback of vasocontraction is lost (Shvetsova et al., 2020). Of note, an altered expression of signaling elements during maturation does not always translate into an altered functional role, as shown with MAP kinases (Gaynullina et al., 2021).
These data have been summarized in three reviews (Gaynullina et al., 2019; Shvetsova et al., 2021; Gaynullina et al., 2022).
Gaynullina, D., Dweep, H., Gloe, T., Tarasova, O.S., Sticht, C., Gretz, N., Schubert, R. (2015). Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development. Sci Rep. 5, 11106 doi: 10.1038/srep11106
Gaynullina, D., Lubomirov, L.T., Sofronova, S.I., Kalenchuk, V.U., Gloe, T., Pfitzer, G., Tarasova, O.S., Schubert, R. (2013). Functional remodelling of arterial endothelium during early postnatal development in rats. Cardiovasc. Res. 99, 612-21.
Gaynullina,D.K., Schubert,R., Tarasova,O.S. (2019). Changes in Endothelial Nitric Oxide Production in Systemic Vessels during Early Ontogenesis. A Key Mechanism for the Perinatal Adaptation of the Circulatory System Int. J. Mol. Sci. 20: 1421
Gaynullina,D.K., Kudryashova,T.V., Vorotnikov,A.V., Schubert,R., Tarasova,O.S. (2021). MAPKs are highly abundant but do not contribute to α1-adrenergic contraction of rat saphenous arteries in the early postnatal period. International Journal of Molecular Sciences 22: 6037
Ma,D., Gaynullina,D.K., Schmidt,N., Mladenov,M., Schubert,R. (2020). The functional availability of arterial Kv7 channels is suppressed considerably by large-conductance calcium-activated potassium channels in 2- to 3-month old but not in 10- to 15-day old rats. Front Physiol 11: 597395
Mochalov,S.V., Tarasova,N.V., Kudryashova,T.V., Gaynullina,D.K., Kalenchuk,V.U., Borovik,A.S., Vorotnikov,A.V., Tarasova,O.S., Schubert,R. (2018). Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity. Acta Physiol 223: e13044
Puzdrova, V.A., Kudryashova, T.V., Gaynullina, D.K., Mochalov, S.V., Aalkjaer, C., Nilsson, H., Vorotnikov, A.V., Schubert, R., Tarasova, O.S. (2014). Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+-sensitivity during early postnatal development in rats. Acta.Physiol. 212, 128-141
Shvetsova,A.A., Gaynullina,D.K., Tarasova,O.S., Schubert,R. (2019). Negative feedback regulation of vasocontraction by potassium channels in 10-to 15-day-old rats: Dominating role of K(v)7 channels Acta Physiol 225: e13176
Shvetsova,A., Gaynullina,D.K., Schmidt,N., Bugert,P., Lukoshkova,E.V., Tarasova,O.S., Schubert,R. (2020). TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1‐ to 2‐week‐old but not adult rats. Br. J. Pharmacol. 177:c5148-5162
Shvetsova,A.A., Gaynullina,D.K., Tarasova,O.S., Schubert,R. (2021) Remodeling of arterial tone regulation in postnatal development: focus on smooth muscle cell potassium channels. International Journal of Molecular Sciences 22: 5413
Gaynullina,D.K., Tarasova,O.S., Shvetsova,A.A., Borzykh,A.A., Schubert,R. (2022) The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis. International Journal of Molecular Sciences 23: 5987
Mechanotransduction mechanisms in vascular smooth muscle cells
We could demonstrate that PKA (Schubert et al., 1999), Rho-kinase (Schubert et al., 2002) and BK as well as Kv7 channels (Sausbier et al., 2005, Ma et al. 2020) contribute to the setting of the level of small artery myogenic tone. Of note, Kv7 channels are limited in their negative feedback on myogenic tone by BK channels and vice versa (Ma et al., 2020). In addition, it was demonstrated that the myogenic response is mediated by Rho-kinase (Schubert et al., 2002) and modulated by neuronal influences (Anschutz & Schubert, 2005). The mechanisms of the myogenic response have been discussed in 4 review articles (Schubert & Mulvany, 1999;Schubert & Brayden, 2005;Schubert et al., 2008;Lidington et al. 2013).
We have been participating in a cooperative study showing that endothelial TRPV4 channels are involved in flow-induced vessel dilations (Kohler et al., 2006). A Kv channel, Kv2.1, was identified to prevent vasomotion and safeguard myogenic reactivity (Här et al., 2023).
Anschutz, S. Schubert, R. (2005). Modulation of the myogenic response by neurogenic influences in rat small arteries. Br.J.Pharmacol. 146, 226-233.
Kohler, R., Heyken, W. T., Heinau, P., Schubert, R., Si, H., Kacik, M., Busch, C., Grgic, I., Maier, T., Hoyer, J. (2006). Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler.Thromb.Vasc.Biol. 26, 1495-1502.
Lidington, D., Schubert, R., Bolz, S.S. (2013). Capitalizing on diversity: an integrative approach towards the multiplicity of cellular mechanisms underlying myogenic responsiveness. Cardiovasc. Res. 97, 404-12.
Ma,D., Gaynullina,D.K., Schmidt,N., Mladenov,M., Schubert,R. (2020). The functional availability of arterial Kv7 channels is suppressed considerably by large-conductance calcium-activated potassium channels in 2- to 3-month old but not in 10- to 15-day old rats. Front Physiol 11: 597395
Sausbier, M., Arntz, C., Bucurenciu, I., Zhao, H., Zhou, X. B., Sausbier, U., Feil, S., Kamm, S., Essin, K., Sailer, C. A., Abdullah, U., Krippeit-Drews, P., Feil, R., Hofmann, F., Knaus, H. G., Kenyon, C., Shipston, M. J., Storm, J. F., Neuhuber, W., Korth, M., Schubert, R., Gollasch, M., Ruth, P. (2005). Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. Circulation 112, 60-68.
Schubert, R. Brayden, J. E. (2005). Stretch-activated cation channels and the myogenic response of small arteries. In Mechanosensitivity in Cells and Tissues pp. 402-417.
Schubert, R., Kalentchuk, V. U., Krien, U. (2002). Rho kinase inhibition partly weakens myogenic reactivity in rat small arteries by changing calcium sensitivity. Am.J.Physiol Heart Circ.Physiol 283, H2288-H2295.
Schubert, R., Lehmann, G., Serebryakov, V. N., Mewes, H., Hopp, H.-H. (1999). cAMP-dependent protein kinase is in an active state in rat small arteries possessing a myogenic tone. Am.J.Physiol. 277, H1145-H1155.
Schubert, R., Lidington, D., Bolz, S. S. (2008). The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. Cardiovasc.Res. 77, 8-18.
Schubert, R. Mulvany, M. J. (1999). The myogenic response: established facts and attractive hypotheses. Clin.Sci. 96, 313-326.
Här,K., Lysenko,N.N., Dimitrova,D., Schlüter,T., Zavaritskaya,O., Kamkin,A.G., Mladenov,M., Grisk,O., Köhler,R., Gagov,H., Schubert,R. (2023) Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries. Cells 12: 1989
Mechanisms of calcium sensitivity regulation
In our experiments we have demonstrated that Rho-kinase is contributing to the myogenic response by increasing the calcium sensitivity of the contractile apparatus (Schubert et al., 2002).
In addition, we have shown that the dilation induced by urocortin is caused by a PKA-mediated alteration of the calcium sensitivity (Lubomirov et al., 2001), associated with a dephosphorylation of MYPT1 and an activation of MLCP (Lubomirov et al., 2006a;Lubomirov et al., 2006b;Pfitzer et al., 2006). Further, we showed that Rho-kinase-mediated calcium sensitivity decreases with maturation (Mochalov et al., 2018).
Of note, for Src kinase, also known to affect calcium sensitivity, we discovered a major role in calcium-dependent pathways of contractility regulation (Zavaritskaya et al., 2017) suggesting that kinases have the potential to differentially affect calcium-sensitivity as well as calcium-dependent pathways.
Our data further demonstrate that sympathetic nerves reduce arterial smooth muscle Ca2+-sensitivity during postnatal development (Puzdrova et al. 2014).
We have been participating in cooperative studies showing that adenosine is increasing the calcium sensitivity of the contractile apparatus via p38 MAP-kinase (Martinka et al., 2008) and that expression of a leucine zipper positive splice variant of MYPT1 results in a higher NO/cGMP/PKG sensitivity of cerebral arteries (Lubomirov et al., 2018).
Lubomirov, L., Gagov, H., Petkova-Kirova, P., Duridanova, D., Kalentchuk, V. U., Schubert, R. (2001). Urocortin relaxes rat tail arteries by a PKA-mediated reduction of the sensitivity of the contractile apparatus for calcium. Br.J.Pharmacol. 134, 1564-1570.
Lubomirov, L. T., Reimann, K., Metzler, D., Hasse, V., Stehle, R., Ito, M., Hartshorne, D. J., Gagov, H., Pfitzer, G., Schubert, R. (2006a). Urocortin-induced decrease in Ca2+ sensitivity of contraction in mouse tail arteries is attributable to cAMP-dependent dephosphorylation of MYPT1 and activation of myosin light chain phosphatase. Circ.Res. 98, 1159-1167.
Lubomirov, L. T., Schubert, R., Gagov, H. S., Duridanova, D. B., Pfitzer, G. (2006b). [Urocortin decreases phosphorylation of MYPT1 and increases the myosin phosphatase activity via elevation of the intracellular level of cAMP]. Biofizika 51, 773-780.
Lubomirov,L.T., Papadopoulos,S., Filipova,D., Baransi,S., Todorović,D., Lake,P., Metzler,D., Hilsdorf,S., Schubert,R., Schroeter,M.M., Pfitzer,G. (2018). The involvement of phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and MYPT1 isoform expression in NO/cGMP mediated differential vasoregulation of cerebral arteries compared to systemic arteries. Acta Physiol 224: e13079
Martinka, P., Lai, E. Y., Fahling, M., Jankowski, V., Jankowski, J., Schubert, R., Gaestel, M., Persson, A. E., Persson, P. B., Patzak, A. (2008). Adenosine increases calcium sensitivity via receptor-independent activation of the p38/MK2 pathway in mesenteric arteries. Acta Physiol (Oxf) 193, 37-46.
Mochalov,S.V., Tarasova,N.V., Kudryashova,T.V., Gaynullina,D.K., Kalenchuk,V.U., Borovik,A.S., Vorotnikov,A.V., Tarasova,O.S., Schubert,R. (2018). Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity. Acta Physiol 223: e13044
Pfitzer, G., Lubomirov, L. T., Reimann, K., Gagov, H., Schubert, R. (2006). Regulation of the crossbridge cycle in vascular smooth muscle by cAMP signalling. J.Muscle Res.Cell Motil. 27, 445-454.
Puzdrova, V.A., Kudryashova, T.V., Gaynullina, D.K., Mochalov, S.V., Aalkjaer, C., Nilsson, H., Vorotnikov, A.V., Schubert, R., Tarasova, O.S. (2014). Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+-sensitivity during early postnatal development in rats. Acta.Physiol. 212, 128-141
Schubert, R., Kalentchuk, V. U., Krien, U. (2002). Rho kinase inhibition partly weakens myogenic reactivity in rat small arteries by changing calcium sensitivity. Am.J.Physiol Heart Circ.Physiol 283, H2288-H2295.
Zavaritskaya,O., Lubomirov,L.T., Altay,S., Schubert,R. (2017) Src tyrosine kinases contribute to serotonin-mediated contraction by regulating calcium-dependent pathways in rat skeletal muscle arteries. Pflugers Arch. 469: 767-777