Cristina Velazquez

University of Puerto Rico, Medical Sciences Campus · Academic Affairs

Depolarization‐secretion coupling is thought to be dependent only on extracellular calcium ([Ca²⁺]o). Ryanodine receptor (RyR)‐sensitive stores in Hypothalamic Neurohypophysial System (HNS) terminals produce sparks of intracellular calcium ([Ca²⁺]i) that are voltage‐dependent. We hypothesized that voltage‐elicited increases in intraterminal calcium...

Significance statement: Alcohol tolerance is a key step toward escalating alcohol consumption and subsequent dependence. Our research aims to make significant contributions toward novel, therapeutic approaches to prevent and treat alcohol misuse by understanding the molecular mechanisms of alcohol tolerance. In our current study, we identify the r...

The large conductance Ca(2+) - and voltage-activated K(+) channel (BK) is an important player in molecular and behavioral alcohol tolerance. Trafficking and surface expression of ion channels contribute to the development of addictive behaviors. We have previously reported that internalization of the BK channel is a component of molecular tolerance...

Co-expression of the auxiliary β1 subunit with the pore forming α subunit of BK dramatically alters apparent calcium sensitivity. Investigation of the mechanism underlying the increase in calcium sensitivity of BK in smooth muscle has concentrated on the energetic effect of β1's interaction with α. We take a novel approach, exploring whether β1 mod...

Tolerance is a well described component of alcohol abuse and addiction. The large conductance voltage- and Ca2+-gated potassium channel (BK) has been very useful for studying molecular tolerance. The influence of association with the β4 subunit can be observed at the level of individual channels, action potentials in brain slices, and finally, drin...

μ-Opioid agonists have no effect on calcium currents (ICa) in neurohypophysial terminals when recorded using the classic whole-cell patch-clamp configuration. However, μ-opioid receptor (MOR)-mediated inhibition of ICa is reliably demonstrated using the perforated-patch configuration. This suggests that the MOR-signaling pathway is sensitive to int...

Oxytocin (OT) and vasopressin (AVP) are released from terminals in the neurohypophysis (NH). These neuropeptides (NP) are contained in large dense core vesicles (LDCV). Ryanodine receptors (RyR) in NH terminals can induce spontaneous focal Ca2+ transients (DeCrescenzo, et al., 2004 J. Neurosci.24:1226-1235), making them ideal for studying the role...

The neuronal calcium- and voltage-activated BK potassium channel is modulated by ethanol, and plays a role in behavioral tolerance in vertebrates and invertebrates. We examine the influence of temporal parameters of alcohol exposure on the characteristics of BK molecular tolerance in the ventral striatum, an important component of brain reward circ...

Release of neurotransmitter is activated by the influx of calcium. Inhibition of Ca(2+) channels results in less calcium influx into the terminals and presumably a reduction in transmitter release. In the neurohypophysis (NH), Ca(2+) channel kinetics, and the associated Ca(2+) influx, is primarily controlled by membrane voltage and can be modulated...

Opioids modulate the electrical activity of magnocellular neurons (MCN) and inhibit neuropeptide release at their terminals in the neurohypophysis. We have previously shown that micro-opioid receptor (MOR) activation induces a stronger inhibition of oxytocin (OT) than vasopressin (AVP) release from isolated MCN terminals. This higher sensitivity of...

Release of neurotransmitter is activated by the influx of calcium. Inhibition of Ca2+ channels results in less calcium influx into the terminal and, presumably, a reduction in transmitter release. In the nerve terminals of the neurohypophysis, voltage-gated calcium channels (VGCC) are primarily controlled by membrane voltage and their activity can...

This thesis details my examination of several mechanisms for modulation of neuropeptide release via voltage-dependent and voltage-independent intraterminal signaling in isolated neurohypophysial terminals. The first part of this work characterizes depolarization-induced neuropeptide release in the absence of extracellular calcium. The goal of this...

Effects of extracellular adenosine tri-phosphate (ATP) on ionic currents were investigated using the perforated-patch whole-cell recording technique on isolated terminals of the Hypothalamic Neurohypophysial System (HNS). ATP induced a current response in 70% of these isolated terminals. This inwardly-rectifying, inactivating current had an apparen...

Localized, brief Ca2+ transients (Ca2+ syntillas) caused by release from intracellular stores were found in isolated nerve terminals from magnocellular hypothalamic neurons and examined quantitatively using a signal mass approach to Ca2+ imaging. Ca2+ syntillas (scintilla, L., spark, from a synaptic structure, a nerve terminal) are caused by releas...