Ivanova-Nikolova, T.T. and Breitwieser, G.E. “Effector contributions to Gβγ-mediated signaling as revealed by muscarinic potassium channel gating.” Journal of General Physiology 1997; 109:245-253: In the heart, the atrial G protein regulated inwardly rectifying potassium (GIRK) channels participate in the autonomic control of heart rate. This work revealed for the first time the complex language used by the GIRK channels in the translation of a simple message of the autonomic nervous system into miniature electrical currents.
Ivanova-Nikolova, T.T., Nikolov, E.N., Hansen, C. and Robishaw, J.D. “Muscarinic K+ channel in the heart. Modal regulation by G protein βγ subunits.” Journal of General Physiology 1998; 112: 199-210: This work investigated the correlation between the intensity of the chemical signal (in this case, the concentration of free G protein in the membrane) and the complex language of the GIRK channel. Based on our findings, we developed the first model of regulation of GIRK channels by G proteins. While highly contested when first published, the predictions of this model continue to hold sixteen years later as the advancement of science technology made it possible for other groups to directly test the predictions of the model.
Nikolov, E.N. and Ivanova-Nikolova, T.T. “Coordination of membrane excitability through a GIRK1 signaling complex in the atria.” Journal of Biological Chemistry 2004; 279: 23630-23636: This work tested the idea that the individual GIRK channels are enveloped into a network of signaling proteins in the membrane of cardiac cells and the channel activity reports not only the intensity of the chemical signals, but also the activation state of the rest of the proteins in the GIRK signaling network. This idea led to the purification of the cardiac signaling network and to identification of GIRK channel signaling partners.
Nikolov, E.N., & Ivanova-Nikolova, T.T. “Functional characterization of a small conductance GIRK channel in rat atrial cells.” Biophysical Journal 2004; 87: 3122-3136: This work characterized a previously unknown GIRK channel in the heart that together with the traditional GIRK channels controls the heart rate. The regulation of the newly identified GIRK channels by G proteins, like the regulation of the traditional GIRK channels, reflected the state of activation of the additional signaling components in the membrane network. These findings suggested that the membrane network identified by us controls the function of many proteins regulated by G protein coupled receptors (GPCRs).
Nikolov, E.N., & Ivanova-Nikolova, T.T. “Dynamic integration of α-adrenergic and cholinergic signals in the atria: Role of GIRK channels.” Journal of Biological Chemistry 2007; 282 (39): 28669-28682. This work investigated the effect of GPCR stimulation on the architecture of the cardiac membrane network. We find that GPCR activation triggers reorganization of the proteins with this network. Furthermore each GPCR triggers different pattern of reorganization in the network. This is the first report of a long-term involvement of a membrane-localized signaling network in GPCR signaling. Since 75% of the current medications used in cardiology and neurology are activating or blocking one or another GPCR in the heart or the brain, the findings suggest new avenues for treatment of many serious medical conditions.
Ivanova-Nikolova, T.T., Nikolov, E.N., Hansen, C. and Robishaw, J.D. “Muscarinic K+ channel in the heart. Modal regulation by G protein βγ subunits.” Journal of General Physiology 1998; 112: 199-210: This work investigated the correlation between the intensity of the chemical signal (in this case, the concentration of free G protein in the membrane) and the complex language of the GIRK channel. Based on our findings, we developed the first model of regulation of GIRK channels by G proteins. While highly contested when first published, the predictions of this model continue to hold sixteen years later as the advancement of science technology made it possible for other groups to directly test the predictions of the model.
Nikolov, E.N. and Ivanova-Nikolova, T.T. “Coordination of membrane excitability through a GIRK1 signaling complex in the atria.” Journal of Biological Chemistry 2004; 279: 23630-23636: This work tested the idea that the individual GIRK channels are enveloped into a network of signaling proteins in the membrane of cardiac cells and the channel activity reports not only the intensity of the chemical signals, but also the activation state of the rest of the proteins in the GIRK signaling network. This idea led to the purification of the cardiac signaling network and to identification of GIRK channel signaling partners.
Nikolov, E.N., & Ivanova-Nikolova, T.T. “Functional characterization of a small conductance GIRK channel in rat atrial cells.” Biophysical Journal 2004; 87: 3122-3136: This work characterized a previously unknown GIRK channel in the heart that together with the traditional GIRK channels controls the heart rate. The regulation of the newly identified GIRK channels by G proteins, like the regulation of the traditional GIRK channels, reflected the state of activation of the additional signaling components in the membrane network. These findings suggested that the membrane network identified by us controls the function of many proteins regulated by G protein coupled receptors (GPCRs).
Nikolov, E.N., & Ivanova-Nikolova, T.T. “Dynamic integration of α-adrenergic and cholinergic signals in the atria: Role of GIRK channels.” Journal of Biological Chemistry 2007; 282 (39): 28669-28682. This work investigated the effect of GPCR stimulation on the architecture of the cardiac membrane network. We find that GPCR activation triggers reorganization of the proteins with this network. Furthermore each GPCR triggers different pattern of reorganization in the network. This is the first report of a long-term involvement of a membrane-localized signaling network in GPCR signaling. Since 75% of the current medications used in cardiology and neurology are activating or blocking one or another GPCR in the heart or the brain, the findings suggest new avenues for treatment of many serious medical conditions.
