Biology subjects

Garland, C. J.

Publications and source records attributed to Garland, C. J..

2 recordsLinked to original sources

bioRxiv2025

Identification of sodium/myo-inositol transporter 1 as a major determinant of arterial contractility

BackgroundAs the sodium/ myoinositol transporter (SMIT1) is a positive regulator of Kv7.4/7.5 channels in arterial smooth muscle we postulated that altering SMIT1 expression could have a major impact upon vascular reactivity. Consequently, this study aimed to characterise the effects of changes of SMIT1 membrane abundance on vascular tone and the molecular mechanisms involved. MethodsIsometric tension recording on 2nd order mesenteric arteries and left anterior coronary arteries from male and female Wistar Han rats. Whole artery membrane potential recording. Single cell and whole artery antibody-based imaging. Morpholino based protein knockdown of SMIT1. ResultsMorpholino-mediated knockdown of SMIT1 enhanced U46619- and methoxamine-mediated contractions of mesenteric artery whilst impairing relaxations to the Kv7 activator ML213, isoprenaline and CGRP. Conversely, augmenting SMIT1 membrane abundance by raising external osmolarity with 150 mM raffinose, impaired receptor-mediated contractions of mesenteric and coronary arteries, augmented relaxations to ML213 and adenosine as well as producing membrane potential hyperpolarisation. Proximity ligation assays revealed that raffinose incubation increased the association of SMIT-Kv7.4/7.5 as well as Kv7.4 and G{beta}{gamma} subunits. The SGK1 inhibitor EMD638683 prevented the raffinose-induced increase in SMIT1 and the anti-contractile effect. ConclusionToggling the membrane abundance of SMIT1 had a dramatic effect on the arterial response to vasonstrictors and vasodilators mediated by greater coordination of Kv7 channels and G{beta}{gamma} subunits. This work identified SMT1-Kv7 channel complexes and SGK1 regulation as key modulators of arterial responsiveness.

cell biology↗

bioRxiv2021

A Multi-proxy assessment of the impact of climate change on Late Holocene (ca 4500-3800 BP) Native American villages of the Georgia coast

Circular shell rings along the Atlantic Coast of southeastern North America are the remnants of some of the earliest villages that emerged during the Late Archaic Period (5000 - 3000 BP). Many of these villages, however, were abandoned during the Terminal Late Archaic Period (ca 3800 - 3000 BP). Here, we combine Bayesian chronological modeling with multiple environmental proxies to understand the nature and timing of environmental change associated with the emergence and abandonment of shell ring villages on Sapleo Island, Georgia. Our Bayesian models indicate that Native Americans occupied the three Sapelo shell rings at varying times with some generational overlap. By the end of the complexs occupation, only Ring III was occupied before abandonment ca. 3845 BP. Ring III also consists of statistically smaller oysters (Crassostrea virginica) that people harvested from less saline estuaries compared to earlier occupations. These data, when integrated with recent tree ring analyses, show a clear pattern of environmental instability throughout the period in which the rings were occupied. We argue that as the climate became unstable around 4300 BP, aggregation at shell ring villages provided a way to effectively manage fisheries that are highly sensitive to environmental change. However, with the eventual collapse of oyster fisheries and subsequent rebound in environmental conditions ca. 3800 BP, people dispersed from shell rings, and shifted to non-marine subsistence economies and other types of settlements. This study provides the most comprehensive evidence correlations between large-scale environmental change and societal transformations on the Georgia coast during the Late Archaic period.

ecology↗