Biomedical subjects

S Moosmang

Publications and source records attributed to S Moosmang.

4 recordsLinked to original sources

PubMed2007

Analysis of calcium channels by conditional mutagenesis.

Ca2+ influx through various ion channels is an important determinant of the cytosolic Ca2+ concentration, which plays a pivotal role in countless cellular processes. The cardiac L-type Ca2+ channel, Ca(v)1.2, represents a major pathway for Ca2+ entry and is in many cells expressed together with other high- and low-voltage-activated Ca2+ channels. This article will focus on the use of conditional transgenic mouse models to clarify the roles of Ca2+ channels in several biological systems. The phenotypes of conditional Ca2+ channel transgenic mice have provided novel, and often unexpected, insights into the in vivo function of L-type and T-type Ca2+ channels as mediators of signaling between cell membrane and intracellular processes in blood pressure regulation, smooth muscle contractility, insulin secretion, cardiac function, sleep, learning, and memory.

Animals↗

PubMed2001

Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues.

Hyperpolarization-activated cation currents (I(h)) have been identified in cardiac pacemaker cells and a variety of central and peripheral neurons. Four members of a gene family encoding hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCN1--4) have been cloned recently. Native I(h) currents recorded from different cell types exhibit distinct activation kinetics. To determine if this diversity of I(h) currents may be caused by differential expression of HCN channel isoforms, we investigated the cellular distribution of the transcripts of HCN1--4 in the murine sinoatrial node, retina and dorsal root ganglion (DRG) by in situ hybridization. In the sinoatrial node, the most prominently expressed HCN channel is HCN4, whereas HCN2 and HCN1 are detected there at moderate and low levels, respectively. Retinal photoreceptors express high levels of HCN1, whereas HCN2, 3 and 4 were not found in these cells. In DRG neurons, the dominant HCN transcript is HCN1, followed by HCN2. We next determined the functional properties of recombinant HCN1--4 channels expressed in HEK293 cells. All four channel types gave rise to I(h) currents but displayed marked differences in their activation kinetics. Our results suggest that the heterogeneity of native I(h) currents is generated, at least in part, by the tissue-specific expression of HCN channel genes.

Animals↗

PubMed2000

Expression of T- and L-type calcium channel mRNA in murine sinoatrial node.

At the cellular level, cardiac pacemaking which sets the rate and rhythm of the heartbeat is produced by the slow diastolic depolarization. Several ion channels contribute to this pacemaker depolarization, including T-type and L-type calcium currents. To evaluate the molecular basis of the currents involved, we investigated the cellular distribution of various low voltage activated (LVA) and high voltage activated (HVA) calcium channel mRNAs in the murine sinoatrial (SA) node by in-situ hybridization. The most prominently expressed LVA calcium channel in the SA node is Ca(v)3.1, whereas Ca(v)3.2 is present at moderate levels. The dominant HVA calcium channel transcript is Ca(v)1.2; only traces of Ca(v)1.3 mRNA are detectable in SA myocytes of mice.

Animals↗

PubMedDate not supplied

Differential distribution of four hyperpolarization-activated cation channels in mouse brain.

Hyperpolarization-activated cation currents, termed I(h), are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse brain was investigated using in situ hybridization. The expression of HCN1 was restricted to the olfactory bulb, cerebral cortex, hippocampus, superior colliculus and cerebellum. In contrast, HCN2 transcripts were found at high levels nearly ubiquitously in the brain, and the strongest signals were seen in the olfactory bulb, hippocampus, thalamus and brain stem. HCN3 was uniformly expressed at very low levels throughout the brain. Finally, HCN4 transcripts were prominently expressed selectively in the thalamus and olfactory bulb. Some neurons expressed two or more HCN channel transcripts including hippocampal pyramidal neurons (HCN1, HCN2 and low levels of HCN 4) and thalamic relay neurons (HCN2 and HCN4). Our results demonstrate that each HCN channel transcript has a unique distribution in the brain. Furthermore, they suggest that the heterogeneity of neuronal I(h) may be, at least in part, due to the differential expression of HCN channel genes.

Amino Acid Sequence↗