Donald G. Welsh

ORCID: 0000-0001-5174-186X
Publications
Citations
Views
---
Saved
---
About
Contact & Profiles
Research Areas
  • Ion channel regulation and function
  • Nitric Oxide and Endothelin Effects
  • Cardiac electrophysiology and arrhythmias
  • Neuroscience and Neuropharmacology Research
  • Connexins and lens biology
  • Receptor Mechanisms and Signaling
  • Ion Channels and Receptors
  • Heart Rate Variability and Autonomic Control
  • Cardiovascular and exercise physiology
  • Photoreceptor and optogenetics research
  • Mitochondrial Function and Pathology
  • Caveolin-1 and cellular processes
  • Neuroscience and Neural Engineering
  • Neurobiology and Insect Physiology Research
  • Ion Transport and Channel Regulation
  • Renin-Angiotensin System Studies
  • Thermoregulation and physiological responses
  • Neural dynamics and brain function
  • Adipose Tissue and Metabolism
  • Nicotinic Acetylcholine Receptors Study
  • Traumatic Brain Injury and Neurovascular Disturbances
  • Erythrocyte Function and Pathophysiology
  • Electrochemical Analysis and Applications
  • Hemoglobin structure and function
  • Barrier Structure and Function Studies

Western University
2015-2024

University of Virginia
2019

University of Calgary
2010-2019

Michigan State University
2019

University of Southampton
2019

Libin Cardiovascular Institute of Alberta
2009-2019

Australian Regenerative Medicine Institute
2019

Monash University
2019

Robarts Clinical Trials
2016

Alexandria University
2014-2015

Elevation of intravascular pressure causes depolarization and constriction (myogenic tone) small arteries arterioles, this response is a key element in blood flow regulation. However, the nature pressure-induced has remained elusive. In present study, we provide evidence that transient receptor potential channel (TRPC6) homologue major role depolarizing to pressure. Antisense oligodeoxynucleotides TRPC6 decreased protein expression greatly attenuated arterial smooth muscle caused by elevated...

10.1161/hh0302.105662 article EN Circulation Research 2002-02-22

We performed intracellular recording with Lucifer yellow dye microinjection to investigate the cellular pathway(s) by which constriction and dilation are conducted along wall of arterioles (diameter 47 ± 1 μm, n = 63) supplying blood flow cheek pouch anesthetized hamsters. At rest, membrane potential ( E m ) endothelial (−36 mV) smooth muscle (−35 cells was not different. Micropipette delivery norepinephrine (NE) or phenylephrine (PE) produced cell depolarization (5–41 vasoconstriction (7–49...

10.1152/ajpheart.1998.274.1.h178 article EN AJP Heart and Circulatory Physiology 1998-01-01

We sought to identify potentially modifiable determinants associated with variability in leptomeningeal collateral status patients acute ischemic stroke. Data are from the Keimyung Stroke Registry. Consecutive M1 segment middle cerebral artery ± intracranial internal carotid occlusions on baseline computed tomographic angiography (CTA) May 2004 July 2009 were included. Baseline and follow-up imaging was analyzed blinded all clinical information. Two raters assessed collaterals CTA by...

10.1002/ana.23906 article EN Annals of Neurology 2013-03-28

Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source ROS, the endothelium arteries but not other vascular beds. recorded characterized ROS-triggered Ca(2+) signals representing influx through single TRPA1 channels, which we called...

10.1126/scisignal.2005659 article EN Science Signaling 2015-01-06

We tested the hypothesis that TRPC3, a member of canonical transient receptor potential (TRP) family channels, mediates agonist-induced depolarization arterial smooth muscle cells (SMCs). In support this hypothesis, we observed suppression SMC TRPC3 expression with antisense oligodeoxynucleotides significantly decreased and constriction intact cerebral arteries in response to UTP. contrast, contraction SMCs induced by increased intravascular pressure, i.e., myogenic responses, were not...

10.1152/ajpheart.00861.2004 article EN AJP Heart and Circulatory Physiology 2004-12-17

Vascular cells communicate electrically to coordinate their activity and control tissue blood flow. To foster a quantitative understanding of this fundamental process, we developed computational model that was structured mimic skeletal muscle resistance artery. Each endothelial cell smooth in our virtual artery treated as the electrical equivalent capacitor coupled parallel with non‐linear resistor representing ionic conductance; intercellular gap junctions were represented by ohmic...

10.1113/jphysiol.2005.090233 article EN The Journal of Physiology 2005-07-08

Strong inward rectifying K(+) (K(IR)) channels have been observed in vascular smooth muscle and can display negative slope conductance. In principle, this biophysical characteristic could enable K(IR) to 'amplify' responses initiated by other conductances. To test this, we characterized the diversity of properties resistance arteries, confirmed presence conductance then determined whether inhibition alters responsiveness middle cerebral, coronary septal third-order mesenteric arteries...

10.1113/jphysiol.2007.145474 article EN The Journal of Physiology 2007-12-07

When arteries constrict to agonists, the endothelium inversely responds, attenuating initial vasomotor response. The basis of this feedback mechanism remains uncertain, although past studies suggest a key role for myoendothelial communication in signaling process. present study examined whether second messenger flux through gap junctions initiates negative-feedback response hamster retractor muscle feed arteries. We specifically hypothesized that when agonists elicit depolarization and rise...

10.1152/ajpcell.00418.2011 article EN AJP Cell Physiology 2012-01-27

L-type Ca(2+) channels are broadly expressed in arterial smooth muscle cells, and their voltage-dependent properties important tone development. Recent studies have noted that these not singularly vascular tissue other subtypes likely present. In this study, we ascertained which voltage-gated rat cerebral determined contribution to the myogenic response. mRNA analysis revealed α(1)-subunit of (Ca(v)1.2) T-type (Ca(v)3.1 Ca(v)3.2) present isolated cells. Western blot subsequently confirmed...

10.1152/ajpheart.00476.2012 article EN AJP Heart and Circulatory Physiology 2012-10-27

T-type (CaV3.1/CaV3.2) Ca(2+) channels are expressed in rat cerebral arterial smooth muscle. Although present, their functional significance remains uncertain with findings pointing to a variety of roles.This study tested whether CaV3.2 mediate negative feedback response by triggering sparks, discrete events that initiate hyperpolarization activating large-conductance Ca(2+)-activated K(+) channels.Micromolar Ni(2+), an agent selectively blocks but not CaV1.2/CaV3.1, was first shown...

10.1161/circresaha.114.304056 article EN Circulation Research 2014-08-02

1. Increases in intravascular pressure depolarize vascular smooth muscle cells. Based on the attenuating effects of Cl- channel antagonists, it has been suggested that swelling-activated channels may be integral to this response. Consequently, study tested for presence a conductance both intact rat cerebral arteries and isolated 2. A 50 mosmol l-1 hyposmotic challenge (300 250 l-1) constricted arteries. This constriction contained all salient features pressure-induced response including cell...

10.1111/j.1469-7793.2000.t01-1-00139.x article EN The Journal of Physiology 2000-08-01

1 In arterioles of the hamster cheek pouch, vasodilatation and vasoconstriction can spread via conduction electrical signals through gap junctions between cells that comprise vessel wall. However, in resistance networks supplying other tissues has received relatively little attention. anaesthetized hamsters, we have investigated dilatation constriction along feed arteries retractor muscle, which is contiguous with pouch. 2 When released from a micropipette, acetylcholine (ACh) triggered...

10.1111/j.1469-7793.1999.283aa.x article EN The Journal of Physiology 1999-04-01

Acetylcholine (ACh) released at the neuromuscular junction (NMJ) triggers muscle fiber contraction. We tested whether this source of ACh also vasodilation. Arterioles [diameter: 4th order (4A), 18 +/- 3 microns; 2nd (2A), 35 2 microns] and feed arteries (60 4 microns) were observed in retractor anesthetized hamsters. During stimulation [25% duty cycle (500-ms train, 1 per s) approximately 40% maximum isometric tension], a nicotinic receptor antagonist (tubocurarine, 10 microM) prevented...

10.1152/ajpheart.1997.273.1.h156 article EN AJP Heart and Circulatory Physiology 1997-07-01

This study examined whether inward rectifying K+ (KIR) channels facilitate cell-to-cell communication along skeletal muscle resistance arteries. With the use of feed arteries from hamster retractor muscle, experiments KIR were functionally expressed and channel blockade attenuated conduction acetylcholine-induced vasodilation, an index communication. Consistent with expression, this observed following: 1) a sustained Ba2+-sensitive, K+-induced dilation in preconstricted arteries; 2)...

10.1152/ajpheart.00217.2006 article EN AJP Heart and Circulatory Physiology 2006-04-15

The molecular identity of receptor-operated, nonselective cation channels (ROCs) vascular smooth muscle (VSM) cells is not known for certain. Mammalian homologues the Drosophila canonical transient receptor potential (TRPCs) are possible candidates. This study tested hypothesis that heteromultimeric TRPC contribute to ROC current A7r5 VSM activated by [Arg 8 ]-vasopressin. expressed transcripts encoding TRPC1, TRPC4β, TRPC6, and TRPC7. TRPC4, TRPC7 protein expression was confirmed...

10.1161/01.res.0000226495.34949.28 article EN Circulation Research 2006-05-12

The smooth muscle cells of resistance arteries depolarize and contract when intravascular pressure is elevated. This a central characteristic myogenic tone, which plays an important role in regulation blood flow many vascular beds. Pressure-induced depolarization depends part on the activation cation channels. Here, we show that these channels pressure-induced are mediated by protein kinase C cerebral arteries. Diacylglycerol, phorbol myristate acetate, cell swelling activate current have...

10.1152/ajpheart.00605.2002 article EN AJP Heart and Circulatory Physiology 2002-12-01

This study examined whether elevated intravascular pressure stimulates asynchronous Ca(2+) waves in cerebral arterial smooth muscle cells and if their generation contributes to myogenic tone development. The endothelium was removed from rat arteries, which were then mounted an arteriograph, pressurized (20-100 mmHg) under a variety of experimental conditions. Diameter membrane potential (V(M)) monitored using conventional techniques; wave myosin light chain (MLC(20))/MYPT1 (myosin...

10.1113/jphysiol.2010.193300 article EN The Journal of Physiology 2010-08-25

The regulation of arterial tone is critical in the spatial and temporal control cerebral blood flow. Voltage-gated Ca2+ (CaV) channels are key regulators excitation–contraction coupling smooth muscle, thereby tone. Although L- T-type CaV have been identified rodent little known about expression function specific subtypes human arteries. Here, we determined which present arteries defined their roles determining Quantitative polymerase chain reaction Western blot analysis, respectively, mRNA...

10.1085/jgp.201511361 article EN The Journal of General Physiology 2015-04-27
Coming Soon ...