Biomedical subjects

K Bielefeldt

Publications and source records attributed to K Bielefeldt.

At least 19 recordsLinked to original sources

PubMed2007

Luminal stimuli acutely sensitize visceromotor responses to distension of the rat stomach.

Inflammation can enhance responses to different stimuli consistent with the development of hypersensitivity. To determine whether sequentially applied stimuli interact, we determined visceromotor responses (VMR) to gastric distension, measured at baseline and 60 min after instillation of saline, glycocholic acid (GCA) or ethanol through a gastrostomy in controls and rats with gastric ulcers. In another series of experiments, chemicals were administered before and 60 min after repeated distension of the stomach. Ethanol, but not saline or GCA, increased VMR in controls with a more significant rise in rats with gastric ulcerations. GCA increased responses to gastric distension in controls, whereas GCA and ethanol enhanced responses to gastric distensions in rats with gastric ulcers. Responses to saline, GCA, or ethanol were not affected by repeated noxious distension of the stomach. Luminal stimuli can trigger visceromotor responses and sensitize gastric afferents to mechanical stimulation, thus potentially contributing to dyspeptic symptoms.

Acetic Acid↗

PubMed2006

Dual mechanisms of angiotensin-induced activation of mouse sympathetic neurones.

Ang II directly activates neurones in sympathetic ganglia. Our goal was to define the electrophysiological basis of this activation. Neurones from mouse aortic-renal and coeliac ganglia were identified as either 'tonic' or 'phasic'. With injections of depolarizing currents, action potentials (APs) were abundant and sustained in tonic neurones (TNs) and scarce or absent in phasic neurones (PNs). Resting membrane potentials were equivalent in TNs (-48 +/- 2 mV, n = 18) and PNs (-48 +/- 1 mV, n = 23) while membrane resistance was significantly higher in TNs. Ang II depolarized and increased membrane resistance equally in both TNs (n = 8) and PNs (n = 8) but it induced APs only in TNs, and enhanced current-evoked APs much more markedly in TNs (P < 0.05). The AT1 receptor antagonist losartan (2 microm, n = 6) abolished all responses to Ang II, whereas the AT2 receptor blocker PD123,319 had no effect. The transient K+ current (IA), which was more than twice as large in TNs as in PNs, was significantly inhibited by Ang II in TNs only whereas the delayed sustained K+ current (IK), which was comparable in both TNs and PNs, was not inhibited. M currents were more prominent in PNs and were inhibited by Ang II. The IA channel blocker 4-aminopyridine triggered AP generation in TNs and prevented the Ang II-induced APs but not the depolarization. Blockade of M currents by oxotremorine M or linopirdine prevented the depolarizing action of Ang II. The protein kinase C (PKC) inhibitor H7 (10 microm, n = 9) also prevented the Ang II-induced inhibition of IA and the generation APs but not the depolarization nor the inhibition of M currents. Conversely, the PKC agonist phorbol 12-myristate 13-acetate mimicked the Ang II effects by triggering APs. The results indicate that Ang II may increase AP generation in sympathetic neurones by inducing a PKC-dependent inhibition of IA currents, and a PKC-independent depolarization through inhibition of M currents. The differential expression of various K+ channels and their sensitivity to phosphorylation by PKC may determine the degree of activation of sympathetic neurones and hence may influence the severity of the hypertensive response.

Action Potentials↗

PubMed2005

Basic and clinical aspects of visceral sensation: transmission in the CNS.

Pain and discomfort are the leading cause for consultative visits to gastroenterologists. Acute pain should be considered a symptom of an underlying disease, thereby serving a physiologically important function. However, many patients experience chronic pain in the absence of potentially harmful stimuli or disorders, turning pain into the primary problem rather than a symptom. Vagal and spinal afferents both contribute to the sensory component of the gut-brain axis. Current evidence suggests that they convey different elements of the complex sensory experience. Spinal afferents play a key role in the discriminatory dimension, while vagal input primarily affects the strong emotional and autonomic reactions to noxious visceral stimuli. Drugs, surgical and non-pharmacological treatments can target these pathways and provide therapeutic options for patients with chronic visceral pain syndromes.

Afferent Pathways↗

PubMed2004

Experimentally induced ulcers and gastric sensory-motor function in rats.

Prior studies have demonstrated that inflammation can sensitize visceral afferent neurons, contributing to the development of hyperalgesia. We hypothesized that both afferent and efferent pathways are affected, resulting in changes in motor and sensory function. Kissing ulcers (KU) were induced in the distal stomach by injecting 60% acetic acid for 45 s into a clamped area of the stomach. In controls, saline was injected into the stomach. A balloon catheter was surgically placed into the stomach, and electromyographic responses to gastric distension were recorded from the acromiotrapezius muscle at various times after ulcer induction. The accommodation reflex was assessed by slowly infusing saline into the distally occluded stomach. Gastric pressure changes in response to vagal stimulation were measured in anesthetized rats. Contractile function of circular muscle strips was examined in vitro using force-displacement transducers. KU caused gastric hypersensitivity that persisted for at least 14 days. Fluid distension of the stomach led to a rapid pressure increase in KU but not in control animals, consistent with an impaired accommodation reflex. Gastric ulcers enhanced the contractile response to vagal stimulation, whereas the effect of cholinergic stimulation on smooth muscle in vitro was not changed. These data suggest that inflammation directly alters gastric sensory and motor function. Increased activation of afferents will trigger vagovagal reflexes, thereby further changing motility and indirectly activating sensory neurons. Thus afferent and efferent pathways both contribute to the development of dyspeptic symptoms.

Acetic Acid↗

PubMed2004

Increased nerve growth factor expression triggers bladder overactivity.

UNLABELLED: Prior studies have demonstrated an association between visceral inflammation, an increase in nerve growth factor (NGF) expression, and development of hyperalgesia. Because multiple mediators are released during inflammatory processes, we examined the effect of NGF alone using viral gene transfer in vivo. Replication-deficient adenoviral vectors encoding for NGF or beta-galactosidase were injected into the bladder wall. NGF levels were determined with an enzyme-linked immunoabsorbance assay. Cystometrograms were obtained 3 and 5 days after gene transfer by using a surgically implanted bladder catheter in awake male rats. Although the treatment with a control virus did not change NGF levels compared with those of naive animals, the vector encoding for NGF increased NGF protein levels in the bladder 4-fold. Histologically, no evidence of inflammation was noted. Expression of NGF led to bladder overactivity, whereas beta-galactosidase expression was without effect. These data demonstrate that a transient increase in NGF expression without associated inflammation sensitizes visceral reflex pathways, leading to bladder overactivity. Treatment strategies targeting NGF signaling might be useful in disorders involving sensitization of peripheral nerves. PERSPECTIVE: Growth factors have been implicated in the pathogenesis of inflammatory pain. This study uses gene transfer to demonstrate that NGF sensitizes afferent pathways in the absence of inflammation, making it a potentially relevant treatment target.

Animals↗

PubMed2003

Gastric ulcers reduce A-type potassium currents in rat gastric sensory ganglion neurons.

Voltage-dependent potassium currents are important contributors to neuron excitability and thus also to hypersensitivity after tissue insult. We hypothesized that gastric ulcers would alter K(+) current properties in primary sensory neurons. The rat stomach was surgically exposed, and a retrograde tracer (1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine methanesulfonate) was injected into multiple sites in the stomach wall. Inflammation and ulcers were produced by 10 injections of 20% acetic acid (HAc) in the gastric wall. Saline (Sal) injections served as control. Nodose or T9-10 dorsal root ganglia (DRG) cells were harvested and cultured 7 days later to record whole cell K(+) currents. Gastric sensory neurons expressed transient and sustained outward currents. Gastric inflammation significantly decreased the A-type K(+) current density in DRG and nodose neurons (Sal vs. HAc-DRG: 82.9 +/- 7.9 vs. 46.5 +/- 6.1 pA/pF; nodose: 149.2 +/- 10.9 vs. 71.4 +/- 11.8 pA/pF), whereas the sustained current was not altered. In addition, there was a significant shift in the steady-state inactivation to more hyperpolarized potentials in nodose neurons (Sal vs. HAc: -76.3 +/- 1.0 vs. -83.6 +/- 2.2 mV) associated with an acceleration of inactivation kinetics. These data suggest that a reduction in K(+) currents contributes, in part, to increased neuron excitability that may lead to development of dyspeptic symptoms.

4-Aminopyridine↗

PubMed2003

Arylacetamide kappa-opioid receptor agonists produce a tonic- and use-dependent block of tetrodotoxin-sensitive and -resistant sodium currents in colon sensory neurons.

We have previously reported that U50,488 [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide] enantiomers contribute to visceral antinociception by a nonopioid receptor-mediated blockade of sodium currents in colon sensory neurons. The present experiments were undertaken to examine the effect of arylacetamide kappa-opioid receptor agonists (kappa-ORAs) U50,488 and EMD 61,753 [(N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2,2-diphenylacetamide HCl] on tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) sodium currents, and the mechanism of their sodium channel-blocking actions. Whole cell patch-clamp experiments were performed on colon sensory neurons from the S1 dorsal root ganglion identified by content of retrograde tracer 1.1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine metanesulfonate. The concentration-response curves of U50,488 and EMD 61,753, for tonic inhibition of total, TTX-S, and TTX-R sodium currents were similar (EC50 values for U50,488 and EMD 61,753 were 8.4 +/- 1.69 and 1.2 +/- 1.78 microM, respectively). In contrast, the peptide kappa-ORA dynorphin was without effect in these experiments. U50,488 (10 microM) shifted the voltage dependence of steady-state inactivation curves for total, TTX-S, and TTX-R currents to more negative potentials. Inhibition was present at holding potentials of -100 to -20 mV. After the tonic block elicited by 10 microM U50,488, repetitive stimulation with 5-ms depolarizing pulses at a frequency of 3 Hz further enhanced the inhibition of total, TTX-R, and TTX-S currents by 43.8 +/- 4.9, 46.2 +/- 4.9, and 40 +/- 3.2%, respectively. These results demonstrate that arylacetamide kappa-ORAs nonselectively inhibit voltage-evoked sodium currents in a manner similar to local anesthetics, by enhancing closed-state inactivation and induction of use-dependent block.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2003

Nerve growth factor and gastric hyperalgesia in the rat.

We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague-Dawley rats (300-400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response.

Acetic Acid↗

PubMed2003

Role of nerve growth factor in modulation of gastric afferent neurons in the rat.

Recent studies demonstrated that experimental ulcers are associated with changes in the properties of voltage-sensitive sodium currents in sensory neurons. We hypothesized that nerve growth factor (NGF) contributes to these changes. Gastric ulcers were induced by acetic acid injection into the wall of the rat stomach. NGF expression was determined by ELISA and immunohistochemically. Sensory neurons were labeled by injection of a retrograde tracer into the gastric wall. Sodium currents were recorded in gastric sensory neurons from nodose and dorsal root ganglia cultured for 24 h in the presence of NGF or a neutralizing NGF antibody, respectively. Gastric ulcer formation caused a rise in NGF concentration within the gastric wall and an increase in NGF immunoreactivity. Exposure to NGF caused a significant increase in the TTX-resistant sodium current, whereas the TTX-sensitive sodium current remained unchanged. This was associated with an acceleration of the recovery from inactivation in spinal sensory neurons. Production and release of NGF in the gastric wall may contribute to sensitization of primary afferent neurons during gastric inflammation.

Anesthetics, Local↗

PubMed2002

Experimental ulcers alter voltage-sensitive sodium currents in rat gastric sensory neurons.

BACKGROUND & AIMS: Voltage-dependent Na+ currents are important determinants of excitability. We hypothesized that gastric inflammation alters Na+ current properties in primary sensory neurons. METHODS: The stomach was surgically exposed in rats to inject the retrograde tracer 1.1'-dioctadecyl-3,3,3,'3-tetramethylindocarbocyanine methanesulfonate and saline (control) or 20% acetic acid (ulcer group) into the gastric wall. Nodose or thoracic dorsal root ganglia (DRG) were harvested after 7 days to culture neurons and record Na+ currents using patch clamp techniques. RESULTS: There were no lesions in the control and 3 +/- 1 ulcers in the ulcer group. Na+ currents recovered significantly more rapidly from inactivation in nodose and DRG neurons obtained from animals in the ulcer group compared with controls. This was partially a result of an increase in the relative contribution of the tetrodotoxin-resistant to the peak sodium current. In addition, the recovery kinetics of the tetrodotoxin-sensitive current were faster. In DRG neurons, gastric inflammation shifted the voltage-dependence of activation of the tetrodotoxin-resistant current to more hyperpolarized potentials. CONCLUSIONS: Gastric injury alters the properties of Na+ currents in gastric sensory neurons. This may enhance excitability, thereby contributing to the development of dyspeptic symptoms.

Acetic Acid↗

PubMed2002

Gastric hyperalgesia and changes in voltage gated sodium channel function in the rat.

Potential peripheral mechanisms that might contribute to the development of visceral hypersensitivity and ultimately to the altered sensations that characterise functional gastrointestinal disorders were examined by developing experimental models of gastric hyperalgesia. A direct link between alteration in behaviour and potential mechanisms of increased excitability of the gastric afferent innervation was found.

Acetic Acid↗

PubMed2001

Angiotensin selectively activates a subpopulation of postganglionic sympathetic neurons in mice.

Angiotensin II (Ang II) increases renal sympathetic nerve activity in anesthetized mice before and after ganglionic blockade, suggesting that Ang II may directly activate postganglionic sympathetic neurons. The present study directly tested this hypothesis in vitro. Neurons were dissociated from aortic-renal and celiac ganglia of C57BL/6J mice. Cytosolic Ca(2+) concentration ([Ca(2+)](i)) was measured with ratio imaging using fura 2. Ang II increased [Ca(2+)](i) in a subpopulation of sympathetic neurons. At a concentration of 200 nmol/L, 14 (67%) of 21 neurons responded with a rise in [Ca(2+)](i). The Ang II type 1 (AT(1)) receptor blocker (losartan, 2 micromol/L) but not the Ang II type 2 (AT(2)) receptor blocker (PD123,319, 4 micromol/L) blocked this effect. The Ang II-induced [Ca(2+)](i) increase was abolished by removal of extracellular Ca(2+) but not altered by depletion of intracellular Ca(2+) stores with thapsigargin. Ang II no longer elicited a [Ca(2+)](i) increase in the presence of lanthanum (25 micromol/L). The specific N-type and L-type Ca(2+) channel blockers, omega-conotoxin GVIA and nifedipine, respectively, significantly inhibited the Ang II-induced [Ca(2+)](i) increase. The protein kinase C inhibitor H7 but not the protein kinase A inhibitor H89 blocked the response to Ang II. These results demonstrate that Ang II selectively activates a subpopulation of postganglionic sympathetic neurons in aortic-renal and celiac ganglia, triggering Ca(2+) influx through voltage-gated Ca(2+) channels. This effect is mediated through AT(1) receptors and requires the activation of protein kinase C. The activation of a subgroup of sympathetic neurons by Ang II may exert unique effects on kidney function in pathological states associated with elevated Ang II.

Angiotensin II↗

PubMed2001

Slow inactivation of sodium currents in the rat nodose neurons.

Nodose neurons express sodium currents that can be differentiated based on their sensitivity to tetrodotoxin. Several studies have demonstrated significant differences in voltage-dependence and kinetics of activation and inactivation between tetrodotoxin-sensitive and tetrodotoxin-resistant currents. However, little is known about the slow inactivation. Using whole cell patch-clamp technique fast and slow inactivation of sodium currents were studied in cultured rat nodose neurons. Tetrodotoxin-resistant currents recovered much more rapidly after a 15-ms depolarization than tetrodotoxin-sensitive currents. However, repeated 5-ms depolarizations at 10 Hz induced a cumulative inhibition that was more prolonged in tetrodotoxin-resistant compared to tetrodotoxin-sensitive currents. Consistent with these findings, slow inactivation proceeded more rapidly and was more complete for the tetrodotoxin-resistant than for tetrodotoxin-sensitive currents. While the voltage-dependence of fast inactivation differed significantly between the pharmacologically distinct currents, the voltage-dependence of slow inactivation was similar for both sodium currents. We conclude that slow inactivation of sodium currents can be triggered by trains of brief depolarizations. The resulting prolonged decrease in membrane excitability may contribute to the different patterns of action potential generation observed in primary afferent neurons.

Action Potentials↗

PubMed2000

Regulation of sodium currents through oxidation and reduction of thiol residues.

Changes in redox state are involved in several physiological and pathophysiological processes. Previous experiments have demonstrated that nitric oxide can function as a reactive oxygen species, inhibiting neuronal sodium currents by nitrosylation of thiol residues. We hypothesized that nitric oxide and thiol oxidizers similarly modulate voltage-dependent sodium currents. Voltage-dependent sodium currents were studied with the whole-cell patch-clamp technique in NB41A3 neuroblastoma cells. The nitric oxide donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine did not affect sodium currents. In contrast, the thiol oxidizers thimerosal and 4,4'-dithiopyridine significantly inhibited sodium currents. The effect of thimerosal persisted after washout, but could be fully reversed by the reducing agent dithiothreitol. Reduced glutathione did not restore the sodium current amplitude when given extracellularly, while intracellular glutathione prevented the inhibitory effect of thimerosal. Pretreatment with the alkylating agent N-ethylmaleimide blocked the inhibitory action of thimerosal. Thiol oxidation caused a shift in the voltage dependence of fast and slow inactivation to more hyperpolarized potentials without concomitant effects on the voltage dependence of activation. Mercaptoethanol and reduced glutathione enhanced sodium currents by shifting the voltage dependence of inactivation to depolarized potentials. These results demonstrate that the oxidation and reduction of thiol residues alters the properties of voltage-sensitive sodium channels and may play an important role in the regulation of membrane excitability.

Animals↗

PubMed2000

Differential effects of capsaicin on rat visceral sensory neurons.

Nodose neurons play an important role in the regulation of visceral function. Recent studies demonstrated that about 80% of these neurons contain messenger RNA for the capsaicin receptor, a heat-sensitive ion channel. Nodose neurons express voltage-sensitive sodium currents that can be differentiated based on their sensitivity to tetrodotoxin. Considering the potential role of tetrodotoxin-resistant sodium currents in somatosensory neurons, sodium channel expression and sodium currents were studied in nodose neurons. The results were correlated with the response to capsaicin. Nodose neurons contain messenger RNA for the tetrodotoxin-resistant sodium channel PN3. Consistent with these findings, about half of the neurons predominantly expressed tetrodotoxin-resistant sodium currents. In 54% (47/87) of the cells, capsaicin triggered an increase in intracellular calcium. Similarly, in 42% (18/43) of the cells, capsaicin elicited an inward current. There was no relationship between cell size (r=0.07) or sodium current properties (r=0.14) and the response to capsaicin. Micromolar concentrations of capsaicin inhibited voltage-dependent sodium, calcium and potassium currents. This effect was use dependent and did not involve the capsaicin receptor. In conclusion, capsaicin changed the excitability of visceral sensory neurons by blocking voltage-dependent ion channels, an effect that may contribute to the analgesic properties of capsaicin.

Action Potentials↗

PubMed1999

Nitric oxide enhances slow inactivation of voltage-dependent sodium currents in rat nodose neurons.

Nitric oxide (NO) can alter neuronal excitability by decreasing the current through voltage-sensitive sodium channels. We hypothesized that NO inhibits sodium currents in part by promoting slow inactivation. We performed whole-cell voltage clamp experiments on sensory neurons from the nodose ganglion. The voltage-dependence of inactivation was determined after stepping the neurons to various potentials between -100 and 30 mV for 200 ms (fast inactivation) and 3 min (slow inactivation) prior to depolarization to 10 mV. NO shifted the voltage of half-inactivation for fast and slow inactivation to more hyperpolarized potentials by 7 and 12 mV, respectively. Sodium currents exhibited a more profound closed state and slow inactivation after exposure to NO. These results demonstrate for the fist time that the slow inactivation of sodium currents is subject to modulation. Due to its effects on fast and slow inactivation, NO may cause a prolonged decrease in neuronal excitability.

Animals↗

PubMed1999

Endothelin-stimulated Ca2+ mobilization by 3T3-L1 adipocytes is suppressed by tumor necrosis factor-alpha.

The cytokine tumor necrosis factor-alpha (TNFalpha) contributes to metabolic changes in disease states such as insulin resistance. However, the mechanism by which TNFalpha alters cellular function in these conditions is poorly understood. Because changes in intracellular calcium concentration plays a critical role in hormone action we investigated the effect of TNFalpha on calcium homeostasis in 3T3-L1 adipocytes. In these studies we show that TNFalpha causes a concentration- and time-dependent decrease in Na+/myo-inositol cotransporter (SMIT) mRNA levels and myo-inositol accumulation as well as a decrease in myo-inositol incorporation into phosphoinositides. These changes coincided with a decrease in endothelin-1-induced phosphatidylinositol (PI) cycle activity in 3T3-L1 adipocytes chronically exposed to TNFalpha. Endothelin-1-induced mobilization of calcium from intracellular stores was also diminished by TNFalpha. The effect of TNFalpha on endothelin-1-induced PI cycle activity and calcium mobilization was not due to a decrease in endothelin receptors. However, TNFalpha did cause a moderate decrease in phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) activity in 3T3-L1 adipocytes. Combined, a decrease in phosphoinositide production and PIP2-specific PLC activity could be responsible for altering PI cycle activity and the generation of the second messenger myo-inositol 1,4,5-trisphosphate, thereby reducing calcium mobilization. Such changes in intracellular signaling may contribute to the pathophysiology of insulin resistance associated with TNFalpha.

3T3 Cells↗

PubMed1999

Molecular diversity of voltage-sensitive calcium channels in smooth muscle cells.

Voltage-sensitive calcium channels play an important role in the excitation-contraction coupling of smooth muscle. Several subunits form the oligomeric channel complex and determine its functional properties. Therefore a differential distribution of the various channel subunits and their splice forms could contribute to the functional specialization of smooth muscle cells. To test this hypothesis, specific primers were designed to amplify messenger ribonucleic acid (mRNA) from vascular and gastrointestinal smooth muscle of the rabbit by reverse transcription and polymerase chain reaction (RT-PCR). The presence of high- and low-threshold voltage-dependent calcium channels was also examined in a smooth muscle-derived cell line (A7R5). Consistent with the physiologic data, smooth muscle contains mRNA for the pore-forming subunits of high- and low-threshold voltage-dependent calcium channels, alpha-1C and alpha-1G. Three splice variants of the alpha-1C-subunit were identified in smooth muscle. These may affect dihydropyridine binding and the interaction between the alpha-1C and the beta-subunit. In addition, three of the four cloned beta-subunits (beta-1b, beta-2, and beta-3) could be found in all smooth muscle tissues examined. These data demonstrate that various splice forms of the L-type calcium channel exist in smooth muscle tissue. Moreover, these experiments also show for the first time that smooth muscle cells contain mRNA for low-threshold voltage-sensitive calcium channels. Combinations of the pore-forming subunits with one of the three beta-subunits could account for functional differences between smooth muscle cells from distinct regions. A better understanding of the structure and function of these channels may help in our understanding of diseases affecting smooth muscle and help in the development of novel drugs targeting these molecules.

Alternative Splicing↗