Evidence That Ca2+ within the Microdomain of the L-Type Voltage Gated Ca2+ Channel Activates ERK in MIN6 Cells in Response to Glucagon-Like Peptide-1

Glucagon like peptide-1 (GLP-1) is released from intestinal L-cells in response to nutrient ingestion and acts upon pancreatic β-cells potentiating glucose-stimulated insulin secretion and stimulating β-cell proliferation, differentiation, survival and gene transcription. These effects are mediated through the activation of multiple signal transduction pathways including the extracellular regulated kinase (ERK) pathway. We have previously reported that GLP-1 activates ERK through a mechanism dependent upon the influx of extracellular Ca2+ through L-type voltage gated Ca2+ channels (VGCC). However, the mechanism by which L-type VGCCs couple to the ERK signalling pathway in pancreatic β-cells is poorly understood. In this report, we characterise the relationship between L-type VGCC mediated changes in intracellular Ca2+ concentration ([Ca2+]i) and the activation of ERK, and demonstrate that the sustained activation of ERK (up to 30 min) in response to GLP-1 requires the continual activation of the L-type VGCC yet does not require a sustained increase in global [Ca2+]i or Ca2+ efflux from the endoplasmic reticulum. Moreover, sustained elevation of [Ca2+]i induced by ionomycin is insufficient to stimulate the prolonged activation of ERK. Using the cell permeant Ca2+ chelators, EGTA-AM and BAPTA-AM, to determine the spatial dynamics of L-type VGCC-dependent Ca2+ signalling to ERK, we provide evidence that a sustained increase in Ca2+ within the microdomain of the L-type VGCC is sufficient for signalling to ERK and that this plays an important role in GLP-1- stimulated ERK activation

JNDS, Volume 20, Number 2

Letter from J. Kenneth Arnette to the editor of the Journal of Near-Death Studies on the topic "Response to Krishnan.

JNDS, Volume 14, Number 2

Article discussing the theory of essence, based on the physics of electromagnetism and quantum mechanics, which solves the problem of interaction resulting from Descartes's dualistic conception of human nature. The theory is empirically based in phenomena consistently reported by near-death experiencers

JNDS, Volume 11, Number 1

Article exploring the classical mind/body problem using instances of the near-death experience (NDE) as experimental data. Comparison of the details of the NDE with predictions from theoretical cosmology shows strong similarities between the two and further strengthens the case for dualism. A theory of human nature is proposed that incorporates these similarities

JNDS, Volume 18, Number 2

Article continuing the construction of a dualistic interactionist theory of the near-death experience (NDE), the theory of essence, which was begun in two previous articles. The present work represents an extension of the theory to the microscopic level of analysis, in order to specify in detail the mechanism of essence-brain interaction and to address some general and specific objections to interactionism and the theory of essence

JNDS, Volume 13, Number 2

Letter J. Kenneth Arnette to the editor of the Journal of Near-Death Studies, responding to another letter to the editor from V. Krishnan