Albert Gonzales

• Ph.D. Biomedical Science
• Professor (Assistant) at University of Nevada School of Medicine

Emerging small non-coding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, such as internal and terminal modifications, that c...

The choroid is the thin, vasculature-filled layer of the eye situated between the sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors in the retina. Illumination of the interior surface of the back of the eye (fundus) is a critical regulator of subretinal fluid homeostasis, which determines the overall sha...

Emerging small noncoding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, such as internal and terminal modifications, that ca...

Pericytes—octopoid-like mural cells with multiple projections that enwrap capillary vessels—play a vital role in regulating blood flow within the capillary microvasculature. Occupying the beginning segments of the capillary network, or post-arteriole region, are ensheathing pericytes, which have multiple, densely-packed projections that completely...

Several hypotheses have been tested to understand whole organ regulation in other organs such as the brain and kidney, but no such hypothesis has yet been proposed for ocular circulations. To some extent resolve this deficit our ex vivo mouse eye perfusion model takes the first step in elucidating the mechanisms controlling the individual component...

The structure and function of ion channels are sensitive to direct interactions with lipids of the membrane and to the biophysical properties of the membrane microenvironment, such that membrane fluidity, lateral pressure profile, and thickness can modulate the channels. Cholesterol plays a significant role in regulating membrane fluidity and is ca...

Arteriolar smooth muscle cells (SMCs) and capillary pericytes dynamically regulate blood flow in the central nervous system in the face of fluctuating perfusion pressures. Pressure-induced depolarization and Ca2+ elevation provide a mechanism for regulation of SMC contraction, but whether pericytes participate in pressure-induced changes in blood f...

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs). However, the mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal-interaction molecule 1...

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs). The mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal-interaction molecule 1), a sing...

Nitric oxide (NO) relaxes vascular smooth muscle cells (SMCs) and dilates blood vessels by increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which stimulates the activity of cGMP-dependent protein kinase (PKG). However, the vasodilator mechanisms downstream of PKG remain incompletely understood. Here, we found that transient...

Pericytes in the brain are candidate regulators of microcirculatory blood flow because they are strategically positioned along the microvasculature, contain contractile proteins, respond rapidly to neuronal activation, and synchronize microvascular dynamics and neurovascular coupling within the capillary network. Analyses of mice with defects in pe...

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs), although the mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal interaction molecule 1...

Alzheimer’s disease (AD) is a leading cause of dementia and a substantial healthcare burden. Despite this, few treatment options are available for controlling AD symptoms. Notably, neuronal activity-dependent increases in cortical cerebral blood flow (functional hyperemia) are attenuated in AD patients, but the associated pathological mechanisms ar...

Significance Capillaries—the most abundant vessels in the circulatory system—deliver O 2 and nutrients to all cells of the body. In the brain and retina, capillaries also act as a sensory web that detects neuronal activity. Here, we demonstrate that pericytes localized at capillary junctions in a postarteriole transitional region possess unique pro...

Alzheimer's diseases and Cerebral amyloid angiopathy are diseases centered on the accumulation of toxic amyloid‐β‐containing plaques leading to the slow and progressive deterioration of the brain. Recent work has linked cardiovascular pathologies with these forms neurodegeneration, whereby vascular dysfunction potentiates the inability to efficient...

K ⁺ ‐dependent activation of capillary endothelial K ir channels initiates a retrograde hyperpolarizing signal that causes upstream arteriolar dilation and increased blood flow into the capillary network. These findings cast capillary networks as dynamic K ⁺ ‐sensing webs that respond to regional brain activity by converting neuronal activity, dete...

Junctional membrane complexes facilitate excitation-contraction coupling in skeletal and cardiac muscle cells by forming subcellular invaginations that maintain close (≤20 nm) proximity of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) with voltage-dependent Ca²⁺ channels in the plasma membrane. In fully differentiated smooth muscle...

Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. W...

Pericytes cover most of the surface area of brain capillaries, and yet their role in controlling cerebral blood flow is controversial. Although pericytes have a distinct morphology from vascular smooth muscle, pericytes at the first and second capillary junctions downstream of the terminal arteriole exhibit many of the same excitation‐contraction c...

In cerebral artery myocytes, close proximity of the sarcoplasmic reticulum (SR) and plasma membrane (PM) creates microdomains where Ca2+ released from the SR attains a concentration sufficient to activate large-conductance Ca2+-activated K+ (BK) and melastatin transient receptor potential 4 (TRPM4) channels; essential regulators of membrane excitab...

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 and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of...

Dopaminergic nuclei in the basal ganglia are highly sensitive to damage from oxidative stress, inflammation, and environmental neurotoxins. Disruption of adenosine triphosphate (ATP)-dependent calcium (Ca2+) transients in astrocytes may represent an important target of such stressors that contributes to neuronal injury by disrupting critical Ca2+-d...

Endothelial cells and smooth muscle cells of resistance arteries mediate opposing responses to mechanical forces acting on the vasculature, promoting dilation in response to flow and constriction in response to pressure, respectively. In this review, we explore the role of TRP channels, particularly endothelial TRPV4 and smooth muscle TRPC6 and TRP...

Rationale: 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. Objective: This study tested whether CaV3.2 channels mediate a negative feedback response by triggering Ca(2+) sparks, discrete eve...

Maintaining constant blood flow in the face of fluctuations in blood pressure is a critical autoregulatory feature of cerebral arteries. An increase in pressure within the artery lumen causes the vessel to constrict through depolarization and contraction of the encircling smooth muscle cells. This pressure-sensing mechanism involves activation of t...

Pericytes are an integral part of the neurovascular unit and likely contribute to the neuronal‐dependent regulation of capillary blood flow. Like vascular smooth muscle cells (VSMCs), pericytes are thought to contract through membrane depolarization and activation of voltage‐dependent calcium channels which then causes focal constrictions of capill...

Activation of the Ca ²⁺ ‐permeable transient receptor potential (TRP) ankyrin (A) channel TRPA1 in the cerebral artery endothelium with electrophilic compounds induces dilation. Endogenous agonists for endothelial TRPA1 have not been reported. We hypothesized that H 2 O 2 is an endogenous agonist for TRPA1 in this tissue. H 2 O 2 can be generated b...

Proliferation of airway smooth muscle cells (ASMC) contributes to the remodeling and irreversible obstruction of airways during severe asthma, but the mechanisms underlying this disease process are poorly understood. Here we tested the hypothesis that Ca2+ influx through the vanilliod (V) transient receptor potential (TRP) channel TRPV4 stimulates...

CaV1.2 (L-type) along CaV3.1/CaV3.2 (T-type) are the principal subtypes of voltage-gated Ca2+ channels (VGCC) expressed in cerebral arterial smooth muscle. While studies have long discerned the functional role of CaV1.2, the physiological significance of CaV3.x expression is uncertain. Recent immunohistochemical analysis noted that CaV3.2 localizes...

Bronchial asthma is a highly prevalent chronic respiratory disease with significant impact on human health. Airway remodeling due to proliferation of airway smooth muscle cells (ASMC) causes irreversible airflow obstruction during asthma, but the underlying molecular mechanisms are unclear. We hypothesized that Ca ²⁺ influx via TRPV4 contributes to...

Ca V 1.2 (L‐type) along Ca V 3.1/Ca V 3.2 (T‐type) are the principal subtypes of voltage‐gated Ca ²⁺ channels (VGCC) expressed in cerebral arterial smooth muscle. While studies have long discerned the functional role of Ca V 1.2, the physiological significance of Ca V 3.x expression is uncertain. Recent immunohistochemical analysis noted that Ca V...

The melastatin transient receptor potential channel TRPM4 is essential for pressure‐induced smooth muscle cell contraction and is activated by Ca ²⁺ released from the SR via inositol trisphosphate receptors (IP 3 R). Endothelium‐derived nitric oxide (NO) activates soluble guanylyl cyclase (sGC) leading to the generation of cyclic guanosine monophos...

Arterial tone is dependent on the depolarizing and hyperpolarizing currents regulating membrane potential and governing the influx of Ca(2+) needed for smooth muscle contraction. Several ion channels have been proposed to contribute to membrane depolarization, but the underlying molecular mechanisms are not fully understood. In this review, we will...

In cerebral artery myocytes, the melastatin transient receptor potential channel TRPM4 is activated by Ca ²⁺ release from proximal inositol trisphosphate receptors (IP 3 R), and is essential for pressure‐induced membrane depolarization and vasoconstriction. Multiple isoforms of three families of phospholipase C (PLC) isoforms are present in vascula...

In cerebral artery smooth muscle cells (SMCs), the melastatin transient receptor potential (TRP) channel TRPM4 is a crucial mediator of pressure‐induced membrane depolarization, and is activated by Ca ²⁺ released from inositol trisphosphate (IP 3 ) receptors located on the sarcoplasmic reticulum. In the current study, we examined the mechanosensiti...

The melastatin transient receptor potential (TRP) channel, TRPM4, is a critical regulator of smooth muscle membrane potential and arterial tone. Activation of the channel is Ca(2+)-dependent, but prolonged exposures to high global Ca(2+) causes rapid inactivation under conventional whole-cell patch clamp conditions. Using amphotericin B perforated...

The melastatin (M) transient receptor potential channel (TRP) channel TRPM4 is a critical regulator of vascular smooth muscle cell membrane potential and contractility. We recently reported that PKCδ activity influences smooth muscle cell excitability by promoting translocation of TRPM4 channel protein to the plasma membrane. Here we further invest...

Agonist-dependent activation of non-selective cation channels belonging to the canonical (C) transient receptor potential (TRP) subfamily has a profound influence on vascular tone (Inoue et al. 2001) and proliferation (Abramowitz & Birnbaumer, 2009) of arterial myocytes, responses that can contribute to cardiovascular diseases such as hypertension...

The melastatin (M) transient receptor potential (TRP) channel TRPM4 mediates pressure and protein kinase C (PKC)-induced smooth muscle cell depolarization and vasoconstriction of cerebral arteries. We hypothesized that PKC causes vasoconstriction by stimulating translocation of TRPM4 to the plasma membrane. Live-cell confocal imaging and fluorescen...

The contractile state of vascular smooth muscle cells is regulated by small changes in membrane potential that gate voltage‐dependent calcium channels. The melastatin transient receptor potential (TRP) channel TRPM4 is a critical mediator of pressure‐induced membrane depolarization and arterial constriction. A recent study shows that the tricyclic...

The regulation of cytosolic free Ca ²⁺ is crucial for controlling smooth muscle contraction. Ca ²⁺ release from sarcoplasmic reticulum (SR) stores contribute to the activation of Ca ²⁺ sensitive ion channels located proximally in the plasma membrane. Regulation of these channels governs membrane potential and the opening of voltage‐gated Ca ²⁺ chan...

The Mediterranean diet may be responsible for lower cardiovascular disease rates in Southern versus Northern European countries. Oregano is used abundantly in Mediterranean cooking, but potential cardiovascular benefits have not been investigated. Carvacrol, present in oregano, activates the transient receptor potential (TRP) cation channels TRPA1...

Canonical transient receptor potential (TRPC) proteins may play a role in regulating changes in intracellular calcium ([Ca(2+)](i)). Human myometrium expresses TRPC4, TRPC1 and TRPC6 mRNAs in greatest relative abundance. Contributions of TRPC4 to increases in [Ca(2+)](i) were assessed in PHM1-41 and primary human uterine smooth muscle (UtSMC) cells...

Although it is well established that changes in endothelial intracellular [Ca(2+)] regulate endothelium-dependent vasodilatory pathways, the molecular identities of the ion channels responsible for Ca(2+) influx in these cells are not clearly defined. The sole member of the ankyrin (A) transient receptor potential (TRP) subfamily, TRPA1, is a Ca(2+...

Localized control of blood flow and arterial constriction in response to changes in intraluminal pressure are dependent on the intrinsic regulation of smooth muscle cell membrane potential. The melastatin transient receptor potential (TRP) channel TRPM4 is highly selective for monovalent cations, is activated by elevated levels of intracellular Ca...

The melastatin Transient Receptor Potential (TRP) channel TRPM4 is vital for pressure‐induced smooth muscle cell (SMC) depolarization and constriction of cerebral arteries. Protein kinase C (PKC) activity contributes to SMC excitability by a number of mechanisms, including TRPM4 activation. Although strong evidence shows a correlation between PKC,...

The melastatin Transient Receptor Potential (TRP) channel TRPM4 mediates pressure‐induced smooth muscle depolarization and vasoconstriction of cerebral arteries. Interestingly, recent reports show that several members of the TRP superfamily are gated by directed movement of channel protein into and out of the plasma membrane. We hypothesized that a...

Increases in endothelial cell [Ca ²⁺ ] initiate the production of vasodilatory factors such as nitric oxide, prostaglandin, and epoxyeicosatrienoic acids. The molecular identities of the ion channels responsible for endothelial cell Ca ²⁺ entry are not well defined. We examined the hypothesis that members of the transient receptor potential (TRP) s...

Membrane depolarization, Ca ²⁺ influx, and activation of the Ca ²⁺ ‐calmodulin pathway for smooth muscle contraction regulate arterial tone. The molecular mechanisms responsible for membrane depolarization in response to vasoconstrictor stimuli have not been fully characterized. We recently demonstrated that the melastatin transient receptor potent...

We combined electrophysiological and freeze-fracture methods to estimate the unitary turnover rate of the gamma-aminobutyric acid (GABA) transporter GAT1. Human GAT1 was expressed in Xenopus laevis oocytes, and individual cells were used to measure and correlate the macroscopic rate of GABA transport and the total number of transporters in the plas...