Biomedical subjects

Colin D McCaig

Publications and source records attributed to Colin D McCaig.

At least 19 recordsLinked to original sources

PubMed2006

The roles of calcium signaling and ERK1/2 phosphorylation in a Pax6+/- mouse model of epithelial wound-healing delay.

BACKGROUND: Congenital aniridia caused by heterozygousity at the PAX6 locus is associated with ocular surface disease including keratopathy. It is not clear whether the keratopathy is a direct result of reduced PAX6 gene dosage in the cornea itself, or due to recurrent corneal trauma secondary to defects such as dry eye caused by loss of PAX6 in other tissues. We investigated the hypothesis that reducing Pax6 gene dosage leads to corneal wound-healing defects. and assayed the immediate molecular responses to wounding in wild-type and mutant corneal epithelial cells. RESULTS: Pax6+/- mouse corneal epithelia exhibited a 2-hour delay in their response to wounding, but subsequently the cells migrated normally to repair the wound. Both Pax6+/+ and Pax6+/- epithelia activated immediate wound-induced waves of intracellular calcium signaling. However, the intensity and speed of propagation of the calcium wave, mediated by release from intracellular stores, was reduced in Pax6+/- cells. Initiation and propagation of the calcium wave could be largely decoupled, and both phases of the calcium wave responses were required for wound healing. Wounded cells phosphorylated the extracellular signal-related kinases 1/2 (phospho-ERK1/2). ERK1/2 activation was shown to be required for rapid initiation of wound healing, but had only a minor effect on the rate of cell migration in a healing epithelial sheet. Addition of exogenous epidermal growth factor (EGF) to wounded Pax6+/- cells restored the calcium wave, increased ERK1/2 activation and restored the immediate healing response to wild-type levels. CONCLUSION: The study links Pax6 deficiency to a previously overlooked wound-healing delay. It demonstrates that defective calcium signaling in Pax6+/- cells underlies this delay, and shows that it can be pharmacologically corrected. ERK1/2 phosphorylation is required for the rapid initiation of wound healing. A model is presented whereby minor abrasions, which are quickly healed in normal corneas, transiently persist in aniridic patients, compromising the corneal stroma.

Animals↗

PubMed2006

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.

Animals↗

PubMed2006

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field.

Although it is known that neuronal growth cones migrate towards the cathode of an applied direct current (DC) electric field (EF), resembling the EF present in the developing nervous system, the underlying mechanism remains unclear. Here, we demonstrate temporally and spatially coordinated roles for the GTPases Rac, Cdc42 and Rho and their effectors. Growth cones of cultured Xenopus embryonic spinal neurons turned towards the cathode but collective inhibition of Rho, Rac and Cdc42 attenuated turning. Selective inhibition of Rho, Cdc42 or Rac signalling revealed temporally distinct roles in steering by an electrical gradient. Rho, Rac and Cdc42 are each essential for turning within the initial 2 hours (early phase). Later, Rho and Cdc42 signals remain important but Rac signalling dominates. The EF increased Rho immunofluorescence anodally. This correlated spatially with collapsed growth cone morphology and reduced anodal migration rates, which were restored by Rho inhibition. These data suggest that anodally increased Rho activity induces local cytoskeletal collapse, biasing growth cone advance cathodally. Collapse might be mediated by the Rho effectors p160 Rho kinase and myosin light chain kinase since their inhibition attenuated early turning. Inhibitors of phosphoinositide 3-kinase, MEK1/2 or p38 mitogen-activated protein kinase (MAPK) did not affect turning behaviour, eliminating them mechanistically. We propose a mechanism whereby Rac and Cdc42 activities dominate cathodally and Rho activity dominates anodally to steer growth cones towards the cathode. The interaction between Rho GTPases, the cytoskeleton and growth cone dynamics is explored in the companion paper published in this issue. Our results complement studies of growth cone guidance by diffusible chemical gradients and suggest that growth cones might interpret these co-existing guidance cues selectively.

Animals↗

PubMed2006

Growth cone steering by a physiological electric field requires dynamic microtubules, microfilaments and Rac-mediated filopodial asymmetry.

Electric fields (EFs) resembling those in the developing and regenerating nervous systems steer growth cones towards the cathode. Requirements for actin microfilaments, microtubules and their interactions during EF growth cone steering have been presumed, but remain unproven. Here, we demonstrate essential roles for dynamic microfilaments and microtubules in cathode-directed migration. Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was attenuated significantly by nanomolar concentrations of the microfilament inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule-destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of filopodia preceded cathodal turning of the growth cone, suggesting an instructive role in EF-induced steering. Lamellipodial asymmetry accompanied turning. Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac, respectively, and, as shown in the companion paper in this issue, peptides that selectively prevented effector binding to the CRIB domains of Cdc42 or Rac abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the Rac peptide suppressed lamellipodium formation, increased the number of filopodia, abolished cathodal filopodial orientation, and prevented cathodal steering. The Cdc42 peptide suppressed filopodium formation, increased lamellipodial area and prevented cathodal steering. The cathodal bias of lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for cathodal steering in the absence of filopodia, but the cathodal bias of filopodia through Rac CRIB activity was necessary for cathodal turning. Understanding the mechanism for cathodal growth cone guidance will enhance the emerging clinical effort to stimulate human spinal cord regeneration through EF application.

Actin Cytoskeleton↗

PubMed2006

Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice.

Hydrocephalus is a common and potentially devastating birth defect affecting the CNS, and its relationship with G protein-coupled receptors (GPCRs) is unknown. We have expressed 2, 4, or 6 copies of a GPCR--the human PAC1 receptor with a 130-kb transgene in the mouse nervous system in a pattern closely resembling that of the endogenous gene. Consistent with PAC1 actions, PKA and PKC activity were elevated in the brains of Tg mice. Remarkably, Tg mice developed dose-dependent hydrocephalus-like characteristics, including enlarged third and lateral ventricles and reduced cerebral cortex, corpus callosum, and subcommissural organ (SCO). Neuronal proliferation and apoptosis were implicated in hydrocephalus, and we observed significantly reduced neuronal proliferation and massively increased neuronal apoptosis in the developing cortex and SCO of Tg embryos, while neurite outgrowth and neuronal migration in vitro remain uncompromised. Ventricular ependymal cilia are crucial for directing cerebrospinal fluid flow, and ependyma of Tg mice exhibited disrupted cilia with increased phospho-CREB immunoreactivity. These data demonstrate that altered neuronal proliferation/apoptosis and disrupted ependymal cilia are the main factors contributing to hydrocephalus in PAC1-overexpressing mice. This is the first report to our knowledge demonstrating that misregulation of GPCRs can be involved in hydrocephalus-related neurodevelopmental disorders.

Animals↗

PubMed2005

Electrical inhibition of lens epithelial cell proliferation: an additional factor in secondary cataract?

Cataract is the most common cause of blindness but is at least curable by surgery. Unfortunately, many patients gradually develop the complication of posterior capsule opacification (PCO) or secondary cataract. This arises from stimulated cell growth within the lens capsule and can greatly impair vision. It is not fully understood why residual lens epithelial cell growth occurs after surgery. We propose and show that cataract surgery might remove an important inhibitory factor for lens cell growth, namely electric fields. The lens generates a unique pattern of electric currents constantly flowing out from the equator and entering the anterior and posterior poles. We show here that cutting and removing part of the anterior capsule as in cataract surgery significantly decreases the equatorial outward electric currents. Application of electric fields in culture inhibits proliferation of human lens epithelial cells. This inhibitory effect is likely to be mediated through a cell cycle control mechanism that decreases entry of cells into S phase from G1 phase by decreasing the G1-specific cell cycle protein cyclin E and increasing the cyclin-Cdk complex inhibitor p27kip1. Capsulorrhexis in vivo, which reduced endogenous lens electric fields, significantly increased LEC growth. This, together with our previous findings that electric fields have significant effects on the direction of lens cell migration, points to a controlling mechanism for the aberrant cell growth in posterior capsule opacification. A novel approach to control growth of lens epithelial cells using electric fields combined with other controlling mechanisms may be more effective in the prevention and treatment of this common complication of cataract surgery.

Animals↗

PubMed2005

Wound healing in rat cornea: the role of electric currents.

Human corneal epithelial cells respond rapidly following injury to restore the integrity of the ocular surface. What stimulates and guides cells to move into the wound to heal? One candidate is the wound-induced electric field. Using vibrating probe techniques, we provide detailed temporal and spatial mapping of endogenous electric currents at rat corneal wounds. We find Cl- and Na+ are the major components of electric currents in rat corneal wounds. Na+ is the major component of ionic transport in the resting (nonwounded) rat cornea and of the wound center leakage current, whereas Cl- is a more important component of the endogenous electrical current at the wound edges. Enhancing or decreasing Cl- flow with clinically approved pharmacological agents such as aminophylline, ascorbic acid, or furosemide increased or decreased endogenous wound electric currents, respectively. These changes in wound currents correlated directly with the rate of wound healing in vivo. Thus, pharmacologically enhancing or decreasing wound-induced electric currents increased and decreased wound healing rate, respectively. This may have wide-reaching and novel therapeutic potential in the management of wound healing and may help explain some mechanistic aspects of the effects of some clinically used agents.

Aminophylline↗

PubMed2005

Controlling cell behavior electrically: current views and future potential.

Direct-current (DC) electric fields are present in all developing and regenerating animal tissues, yet their existence and potential impact on tissue repair and development are largely ignored. This is primarily due to ignorance of the phenomenon by most researchers, some technically poor early studies of the effects of applied fields on cells, and widespread misunderstanding of the fundamental concepts that underlie bioelectricity. This review aims to resolve these issues by describing: 1) the historical context of bioelectricity, 2) the fundamental principles of physics and physiology responsible for DC electric fields within cells and tissues, 3) the cellular mechanisms for the effects of small electric fields on cell behavior, and 4) the clinical potential for electric field treatment of damaged tissues such as epithelia and the nervous system.

Animals↗

PubMed2004

DC electric fields induce distinct preangiogenic responses in microvascular and macrovascular cells.

OBJECTIVE: Electrical stimulation induces significant angiogenesis in vivo. We have shown recently that electrical stimulation induces directional migration, reorientation, and elongation of macrovascular endothelial cells. Because angiogenesis occurs mainly in the microvasculature, we have extended this observation to include human microvascular endothelial cells (HMEC-1s) and compared the responses with that of vascular fibroblasts and smooth muscle cells and human umbilical vein endothelial cells. METHODS AND RESULTS: Four types of vascular cells were cultured in electric fields (EFs). Dynamic cell behaviors were recorded and analyzed with an image analyzer. EFs of 150 to 400 mV/mm induced directed migration, reorientation, and elongation of all the vascular cells. HMEC-1s showed the greatest directional migration (migration rate of 11 microm/h and directedness of 0.35 at 200 mV/mm). Most intriguingly, HMEC-1s migrated toward the cathode, whereas the other cell types migrated toward the anode. CONCLUSIONS: Endothelial cells derived from angiogenic microvascular as opposed to nonangiogenic macrovascular tissues were more responsive to electrical stimulation. This intriguing directional selectivity indicates that a DC electrical signal as a directional cue may be able to play a role in the spatial organization of vascular structure.

Animals↗

PubMed2004

Insulin, not leptin, promotes in vitro cell migration to heal monolayer wounds in human corneal epithelium.

PURPOSE: To investigate the effects of insulin and leptin on in vitro wound healing of transformed human corneal epithelial cell monolayers and to identify cellular (migration versus proliferation) and intracellular signaling mechanisms. METHODS: Scratch wounds were created in monolayers of an immortalized human corneal epithelial cell (HCEC) line. The wounded monolayers were exposed to insulin and leptin. Wound areas were measured every hour after wounding for up to 8 hours. Phosphoinositide 3-kinase (PI3-kinase) and mitogen-activated protein (MAP)-kinase signaling was analyzed with Western blot. The actions of insulin were also examined after incubation with inhibitors to extracellular signal regulated kinase (ERK 1/2) and PI3-kinase. RESULTS: The presence of insulin, but not leptin facilitated closure of wounds created in corneal epithelial cell monolayers. Phosphorylation of ERK 1/2 and Akt was stimulated after exposure of the monolayers to insulin. Inhibitors of PI3-kinase and ERK 1/2 prevented or reduced insulin-induced corneal wound healing, respectively. CONCLUSIONS: Exposure of corneal epithelium to insulin facilitated closure of in vitro small wounds through enhanced cell migration instead of proliferation, which depended on ERK 1/2 and PI3-kinase signaling. These data suggest a mechanism by which insulin may influence corneal wound healing in vitro. In vivo, disruptions to the insulin signaling pathway observed in diseases such as diabetes might account for the delayed wound healing and corneal defects.

Blotting, Western↗

PubMed2003

Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors.

Controlling angiogenesis is crucial. Growth factors and cytokines are key regulators but a full understanding remains elusive. Endogenous electrical potential differences exist within and around the vasculature, both in relation to blood flow and in situations where active angiogenesis occurs, such as wound healing, development and tumor growth. Recent work shows that electrical stimulation induces significant angiogenesis in vivo, through enhanced vascular endothelial growth factor (VEGF) production by muscle cells. We report that applied electric fields (EFs) of small physiological magnitude directly stimulate VEGF production by endothelial cells in culture without the presence of any other cell type. EFs as low as 75-100 mV mm-1 (1.5-2.0 mV across an endothelial cell) directed the reorientation, elongation and migration of endothelial cells in culture. These pre-angiogenic responses required VEGF receptor activation and were mediated through PI3K-Akt and Rho-ROCK signaling pathways, resulting in reorganization of the actin cytoskeleton. This indicates that endogenous EFs might play a role in angiogenesis in vivo by stimulating the VEGF receptor signaling pathway, to induce key pre-angiogenic responses. In addition, it raises the feasibility of using applied EFs to initiate and guide angiogenesis through direct effects on endothelial cells.

Acute-Phase Proteins↗

PubMed2003

Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation.

Vascular endothelial cell (VEC) proliferation is a key event in angiogenesis and is tightly regulated. Electric potential differences exist around the vascular endothelium and give rise to endogenous electric fields (EFs), whether these EFs influence VEC proliferation is unclear. We exposed cultured VECs to applied EFs of physiological strengths for up to 72 h. EF at 50 or 100 mV/mm did not influence cell proliferation, but at 200 mV/mm, cell density, cell growth rate, and mitosis index decreased significantly. EF-induced reduction in VEC proliferation was not due to increased apoptosis, because caspase apoptosis inhibitor Z-VAD-FMK (20 microM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G1 phase, as shown by flow cytometry. Western blot showed that EFs decreased G1-specific cyclin E expression and increased cyclin/cyclin-dependent kinase complex inhibitor p27kipl expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G1 by down-regulation of cyclin E expression and up-regulation of p27kipl expression, rather than by promoting apoptosis. If control of the cell cycle by endogenous EFs extends beyond VECs, this would be of widespread biological significance in vivo.

Animals↗

PubMed2003

Bi-directional migration of lens epithelial cells in a physiological electrical field.

An endogenous electric field (EF) exists in the vertebrate lens, but the influences of this on the functions of lens epithelial cells (LECs) are unclear. Because LECs from different regions experience different patterns of endogenous EFs and show striking differences in morphology and function, bovine LECs from different regions were cultured in an applied EF to mimic that occurring naturally. The migration of LECs from central and peripheral regions was both stimulated and directed by an applied EF. Field-directed cell migration required serum, or growth factors. Cells cultured in serum free medium lost directed migration completely and this was restored partially by the addition of basic fibroblast growth factor. The direction of cell migration depended on both EF-strength and the origin of the LECs. Both central and peripheral LECs moved anodally at 150-250mVmm(-1). In a low EF (50mVmm(-1)), peripheral LECs migrated in the opposite direction, cathodally, but central LECs did not respond. Peripheral LECs alone therefore showed field strength dependent, bi-directional migration. A physiological EF enhanced activation of ERK1/2, a signaling molecule in the MAP kinase pathway, and this also required serum. Interestingly, expression of active ERK1/2 was enhanced in peripheral LECs at both 50 and 200mVmm(-1), which stimulated migration in different directions. In central LECs, which showed directed migration only at higher EFs, active ERK1/2 was increased only at 200mVmm(-1). The MAP kinase inhibitor U0126 prevented activation of ERK1/2 in LECs and inhibited EF-directed migration, implicating MAP kinase signaling in directing the migration of LECs in a physiological EF.

Animals↗

PubMed2003

Direct visualization of a stratified epithelium reveals that wounds heal by unified sliding of cell sheets.

Observing cells in their original niche is a key link between the information gleaned from planar culture and in vivo physiology and pathology. A new approach combining the transparency of the cornea, Hoffman modulation optics, and digital imaging allowed movements of individual corneal cells to be viewed directly in situ. 3-Dimensional time-lapse movies imaging unstained cells within the stratified corneal epithelium during wound healing were made. Tracking cell movements dynamically provided a definitive answer to the long-standing question: does a stratified epithelium heal by "sliding" of cell sheets as a coherent unit or do individual cells "leap frog" each other at the wound margin? A wound in the corneal epithelium healed primarily by sliding of the whole epithelium, with approximately 95% of cells moving with similar speed and trajectories and with little change in their relative position. Only 5% of cells changed layers, with equal proportions moving up or down. Epithelial healing in situ occurred in three phases: a latency, migration, and reconstruction phase. This model provides a unique system to study the behaviors of individual cells in their original niche. It shows that cells slide into a wound as a unified unit to heal a stratified epithelium.

Animals↗

PubMed2003

Electric fields and MAP kinase signaling can regulate early wound healing in lens epithelium.

PURPOSE: To use lens epithelial cell monolayer wounds as a model system for the aberrant cell migration underlying posterior capsule opacification (PCO) and to investigate the effects of an applied physiological electric field (EF) on monolayer wound healing. METHODS: Scratch wounds were made in cultured bovine lens epithelial monolayers, and the wounds were exposed to an EF, with or without U0126 treatment (an inhibitor of active extracellular signal-regulated kinase [ERK 1/2]). Serial wound images were taken and wound areas were measured. Western blot analysis and immunocytochemical staining for ERK 1/2 in the wounded monolayers were performed. RESULTS: An applied EF of a given polarity influenced the healing of lens epithelial monolayer wounds. Wounds facing the anode healed at normal rates, those facing the cathode closed much more slowly. U0126, an inhibitor of mitogen-activated protein kinase (MAPK) signaling, inhibited wound healing, with or without exposure to an EF. Western blot analysis showed that both wounding and application of an EF enhanced the activation of ERK 1/2 independently and that U0126 completely inhibited these activations of ERK 1/2 in monolayers. Immunocytochemical staining showed an asymmetric activation of ERK 1/2 in EF-exposed wounds, with much weaker fluorescence in cathode-facing wounds, which could contribute to differentially directed wound-healing rates in an EF. CONCLUSIONS: Exposure to an EF inhibited the healing of lens epithelial monolayer wounds facing the cathode. ERK signaling pathways were involved in healing of lens epithelial monolayer wounds and in the EF-directed migration of the wound edge. It may be possible to use an applied EF to regulate the aberrant migration of lens epithelial cells that results in PCO after cataract surgery.

Animals↗

PubMed2003

HGF, MAPK, and a small physiological electric field interact during corneal epithelial cell migration.

PURPOSE: To investigate the effects of hepatocyte growth factor (HGF) and a small applied electric field (EF) on corneal epithelial cell (CEC) migration. METHODS: Primary cultures of bovine CECs were exposed to an EF (25-250 mV/mm) in the presence or absence of HGF (100 ng/mL). The rate and directionality of CEC migration were quantified. The expression of HGF receptors (HGFRs), p42/44 mitogen-activated protein kinase (MAPK) and the time-course of activation of p42/44 MAPK were investigated by confocal microscopy and Western blot analysis. RESULTS: CECs migrated significantly faster in the presence of an EF, HGF, or HGF and an EF combined. The distribution of HGFRs was intracellular and in the presence of an EF was concentrated in the cathode-facing side. This EF-induced asymmetrical accumulation of HGFRs correlated with the direction of CEC migration. The application of HGF or an EF led to the activation of the MAPK signaling pathway and in the presence of an EF, activation of MAPK was greater in the cathode-facing half of the CECs. Inhibition of the MAPK signaling pathway by PD98059 (100 micro M) reduced the ability of HGF and an EF to enhance the rate of CEC migration, but did not alter EF-induced cathodal directionality. CONCLUSIONS: These data suggest that both HGF and an EF augment the rate of CEC migration through activation of p42/44 MAPK. Moreover, EF-induced redistribution of HGFRs and asymmetry of MAPK signaling, although not instrumental in directing CEC migration cathodally, may be important for the signaling and maintenance of migration.

Animals↗

PubMed2002

Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo.

Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and frequency of cell division in vivo is a naturally occurring, wound-induced electric field (EF). Wounds in rat corneas generate endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; +40 mV internally positive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.

Aminophylline↗

PubMed2002

Genetic analysis of the role of G protein-coupled receptor signaling in electrotaxis.

Cells display chemotaxis and electrotaxis by migrating directionally in gradients of specific chemicals or electrical potential. Chemotaxis in Dictyostelium discoideum is mediated by G protein-coupled receptors. The unique Gbeta is essential for all chemotactic responses, although different chemoattractants use different receptors and Galpha subunits. Dictyostelium amoebae show striking electrotaxis in an applied direct current electric field. Perhaps electrotaxis and chemotaxis share similar signaling mechanisms? Null mutation of Gbeta and cAMP receptor 1 and Galpha2 did not abolish electrotaxis, although Gbeta-null mutations showed suppressed electrotaxis. By contrast, G protein signaling plays an essential role in chemotaxis. G protein-coupled receptor signaling was monitored with PHcrac-green fluorescent protein, which translocates to inositol phospholipids at the leading edge of cells during chemotaxis. There was no intracellular gradient of this protein during electrotaxis. However, F-actin was polymerized at the leading edge of cells during electrotaxis. We conclude that reception and transduction of the electrotaxis signal are largely independent of G protein-coupled receptor signaling and that the pathways driving chemotaxis and electrotaxis intersect downstream of heterotrimeric G proteins to invoke cytoskeletal elements.

Actins↗