ChanTest Channel Panels
Functional ion channel assays grouped by therapeutic area, family and safety
ChanTest’s Ion Channel portfolio includes over 90 targets. This target list has been organized into Ion Channel Panels™ based on current scientific findings, and can help guide functional, manual and automated ion channel screens by therapeutic target for profiling and safety assessment. Check back regularly for an updated listing of available targets.
The voltage-gated cardiac potassium channel, hERG, is responsible for the rapid delayed rectifier current (IKr) that regulates repolarization of the action potential. Inhibition of IKr is the most common cause of delayed repolarization and QT prolongation by non-cardiac drugs and is associated with a potentially fatal ventricular arrhythmia, torsade de pointes. However, the influence of hERG inhibition on the QT interval can be blunted by compensatory inhibition of ion channels that carry depolarizing currents (e.g., Nav1.5 and Cav1.2) that regulate the plateau phase of the action potential. Moreover, delayed repolarization via inhibition of other sources of potassium current (e.g., Kv4.3, KvLQT1/minK, and Kir2.1) may augment or supplant hERG inhibition as a cause of QT prolongation. Drug-induced increase in Nav1.5 current can also delay repolarization and prolong QT. ChanTest’s Cardiac Channel Panel™ assay provides off-target profiling of the major channels that influence ventricular action potential duration. Additionally, the panel provides profiling of channels that regulate heart rate (e.g., HCN2, HCN4: pacemaker current; and Kir3.1/Kir3.4: ACh-activated current; and Cav3.2: T-type calcium current), atrial repolarization (Kv1.5), and response to metabolic stress (Kir6.2/SUR2A: IK,ATP).
| Family | Target | Validation* |
|---|---|---|
| Calcium, Voltage-Gated | Cav1.2/β2/α2δ1 | IWQ, MP, PX, QP |
| Cav1.3/β3/α2δ1 | FLP | |
| Cav3.2 | IWQ, PX | |
| Exchanger | NCX1 Na+/Ca2+ | FLP |
| Hyperpolarization-gated | HCN2 | IWQ, PX, QP |
| HCN4 | IWQ, QP | |
| Ligand-Gated | P2X4 | FLP, PX, QP |
| Potassium, Inward Rectifier | Kir2.1 | IWQ, QP |
| Kir3.1/Kir3.4 | PX | |
| Kir6.2/SUR2A | PX, QP | |
| Potassium, Voltage-Gated | Kv1.5 | IWQ, QP |
| Kv11.1 | IWQ, QP | |
| Kv4.3 | IWQ, PX, QP | |
| Kv7.1 | IWQ, MP, QP | |
| Sodium, Voltage-Gated | Nav1.5 | IWQ, PX, QP |
| TRP | TRPC1 | MP |
| TRPM4 | FLP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Several ion channels have been shown to be upregulated in cancer cells and may be integral to the mechanism of cancer cell proliferation and tumor growth. These channels have been proposed as cancer markers, and channel blockers are in development as tumor growth inhibitors. ChanTest’s Cancer Ion Channel Panel™ includes many of the ion channels that have been linked to cancer cell proliferation including voltage-gated potassium channels (Kv1.3, Kv1.5, EAG1, and hERG1), voltage-gated sodium channels (Nav1.5 and Nav1.7), and calcium-activated potassium channels (BK and IK) that are upregulated in various forms of cancer. Finally, Ca2+ influx through Ca-permeable channels elevates intracellular Ca2+ concentration and serves to trigger cell proliferation. The channel panel includes both voltage-gated Ca2+ channels (Cav1.2 and Cav3.2) as well as TRP channels, that are highly expressed in cancer cells and provide a significant Ca2+ influx.
| Family | Target | Validation* |
|---|---|---|
| Calcium, Voltage-Gated | Cav1.2/β2/α2δ1 | IWQ, MP, PX, QP |
| Cav3.2 | IWQ, PX | |
| Ligand-Gated | a3/β4 | FLP |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa3.1 | PX, QP | |
| Potassium, Voltage-Gated | Kv1.3 | IWQ |
| Kv1.5 | IWQ, QP | |
| Kv11.1 | IWQ, QP | |
| Sodium, Voltage-Gated | Nav1.5 | IWQ, PX, QP |
| Nav1.7 | IWQ, PX, QP | |
| TRP | TRPC6 | FLP, MP |
| TRPM8 | FLP, MP, PX, QP | |
| TRPV1 | FLP, MP | |
| TRPV6 | MP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
The cardiovascular panel includes ion channels that regulate blood flow primarily by vasodilation/constriction of blood vessels; cardiac ion channels that control heart function are found in the Cardiac Channel Panel™. Physiological regulation of vascular resistance relies on the control of Ca2+-dependent contraction of the smooth muscle that surrounds the endothelial cell lining of the vessel lumen. Control of smooth muscle tension involves a variety of Ca2+-permeable channels (e.g., Cav1.2, P2X4, nAChRα7, and most TRP-channels), as well as channels that regulate release of vasoactive substances, and channels that regulate arterial tone via control of membrane potential (K+-selective channels: BK, SK3, IK, Kir2.1, Kir6.1, Kv1.5, and Kv7.1; and a non-selective channel: TRPM4). Under pathological conditions (e.g., vascular inflammation, chronic hypertension, heart failure, or hypoxia) decreased vascular integrity, increased endothelial permeability, and hyperplasia may compromise vascular function. Ion channels involved in pathological mechanisms include Kv7.1, nAChRα7, and several TRP-channels. Thus, the Vascular Panel represents a selection of channels that are potential therapeutic targets for conditions such as hypertension, atherosclerosis, and heart failure. Moreover, drug-induced channel dysfunction may be responsible for adverse effects.
| Family | Target | Validation* |
|---|---|---|
| Calcium, Voltage-Gated | Cav1.2/β2/α2δ1 | IWQ, MP, PX, QP |
| Cav1.3/β3/α2δ1 | FLP | |
| Exchanger | NCX1 Na+/Ca2+ | FLP |
| Ligand-Gated | nAChR α7 | FLP, QP |
| P2X4 | FLP, PX, QP | |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa2.3 | FLP | |
| KCa3.1 | PX, QP | |
| Potassium, Inward Rectifier | Kir2.1 | IWQ, QP |
| Potassium, Voltage-Gated | Kv1.3 | IWQ |
| Kv1.5 | IWQ, QP | |
| Kv7.1 | IWQ, MP, QP | |
| TRP | TRPC1 | MP |
| TRPC6 | FLP, MP | |
| TRPM4 | FLP | |
| TRPV1 | FLP, MP | |
| TRPV4 | FLP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Channels that control urinary bladder contractility and are targets for urinary incontinence treatment include KCa1.1 (BK), a calcium-activated potassium channel, and P2X1, a purinergic receptor-channel. KCa1.1 agonists that promote relaxation also have been investigated for treatment of overactive bladder. TRPM8 channels expressed in bladder afferent nerves are potential targets for treatment of both overactive bladder and painful bladder syndrome. TRPV1 channels expressed in afferent nerve endings, have been investigated as potential targets for treatment of neurogenic urinary incontinence. Relaxation of the corpus cavernosum smooth muscle, essential for erectile function, is controlled by KCa1.1, and agonists are therapeutic targets for erectile dysfunction.
| Family | Target | Validation* |
|---|---|---|
| Ligand-Gated | P2X1 | FLP |
| P2X3 | FLP | |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa3.1 | PX, QP | |
| Potassium, Inward Rectifier | Kir1.1 | MP |
| TRP | TRPM8 | FLP, MP, PX, QP |
| TRPV1 | FLP, MP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Ion channels control metabolic processes such as hormone secretion, gut motility, and electrolyte balance. ChanTest’s Metabolic and Gastro-Intestinal Channel Panel™ includes channels that regulate insulin secretion and are potential therapeutic targets for diabetes and obesity: voltage-gated potassium channel Kv1.3, and the ATP-sensitive potassium channel Kir6.2/SUR1. The panel also includes chloride channels that regulate electrolyte balance (CFTR) for potential treatment of diarrhea. Inflammatory bowel disease targets include the transient receptor potential vanilloid receptor, TRPV1 and the purinergic receptor-channel P2X3. Finally, the ionotropic serotonin receptor 5-HT3A represents a potential target for treatment of irritable bowel syndrome.
| Family | Target | Validation* |
|---|---|---|
| Chloride | CFTR | IWQ, QP |
| ClC-2 | PX | |
| Ligand-Gated | 5-HT3A | FLP, IWQ, MP, PX |
| P2X1 | FLP | |
| P2X3 | FLP | |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| Potassium, Voltage-Gated | Kv1.3 | IWQ |
| TRP | TRPV1 | FLP, MP |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Neurodegeneration-Stroke Channel Panel™
Voltage-gated sodium and potassium channels are potential neuroprotective therapeutic targets in ischemic stroke. The metabolism-sparing effects of sodium channel blockade (e.g., Nav1.1, 1.2, and 1.6) or potassium channel activation (e.g., KCNQ2-5) may confer neuroprotection. Blockade of acid-induced Ca2+ influx via ASIC (acid-sensing ion channels) also may prevent ischemic neuronal damage. Neurodegenerative diseases result in the progressive deterioration of nerve cells. Ion channels in both the central and peripheral nervous systems have been implicated in either the treatment or etiology of neurodegenerative diseases such as multiple sclerosis and Alzheimer’s disease. As indicated in Table 1, neurologic symptoms of Alzheimer’s disease may be treated by blockade of voltage-gated potassium channels (e.g., Kv3.4) and glutamate receptors (e.g., NMDA), or activation of nicotinic acetylcholine receptors (e.g., nAChRα7). Ion channels involved in the etiology or treatment of multiple sclerosis include Nav1.6, Kv1.3, and Kv1.5 .
| Family | Target | Validation* |
|---|---|---|
| Acid-Sensing | ASIC1a | PX |
| ASIC2a | PX | |
| ASIC3 | PX, QP | |
| Calcium, Voltage-Gated | Cav1.3/β3/α2δ1 | FLP |
| Ligand-Gated | nAChR α7 | FLP, QP |
| NMDA (NR1/NR2A) | FLP | |
| NMDA (NR1/NR2B) | FLP | |
| NMDA (NR1/NR2C) | FLP | |
| NMDA (NR1/NR2D) | FLP | |
| Potassium, Calcium-Activated | KCa2.1 | MP |
| KCa2.2 | FLP, MP | |
| KCa2.3 | FLP | |
| Potassium, Voltage-Gated | Kv1.1 | IWQ, PX, QP |
| Kv1.3 | IWQ | |
| Kv1.5 | IWQ, QP | |
| Kv3.4 | IWQ, PX | |
| Kv7.2/Kv7.3 | FLP, PX, QP | |
| Sodium, Voltage-Gated | Nav1.1 | IWQ, QP |
| Nav1.2 | IWQ, QP | |
| Nav1.6 | IWQ, PX, QP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Pain-Inflammation Channel Panel™
Ion channels in both the central and peripheral nervous systems have been linked to pain. Pain sensation is mediated by ion channels in nerve endings (e.g., TRPA1, TRPV1, TRPM8, and P2X2-4) that trigger pain input to the CNS via the dorsal root ganglia neurons (DRG). Impulses in the DRG are conducted by sodium channels (e.g., Nav1.1, Nav1.7, Nav1.8, and Nav1.9) and transmitted at synapses on neurons in the dorsal horn of the spinal cord. In the dorsal horn, voltage-gated calcium channels (Cav2.2) control the release of neurotransmitter (glutamate) to excite post-synaptic glutamate receptors (NMDAR) and trigger signaling to higher centers. In the brain, pain signals are processed by neurons that are regulated by both repolarizing (e.g., Kv1.4, Kv4.2, and KCNQ2/KCNQ3) and depolarizing (e.g., Nav1.2, Nav1.3, HCN1, Cav2.1, Cav2.2, Cav3.2, and NMDAR) channels. Hypersensitivity in neuropathic and inflammatory pain has been linked to changes in the expression and/or function of a variety of channels (Table 1) that can be either therapeutic or adverse event targets.
Channels that regulate inflammatory/immune responses include potassium channels (e.g., Kv1.3, and KCa3.1), TRP channels (e.g., TRPC4, TRPM4), purinergic receptor-channels (e.g., P2X7), and ligand-gated channels (e.g., the nicotinic acetylcholinergic receptor, nAChRα7). These channels have been targeted for potential therapeutic suppression of pathological immune response in several disease states .
| Family | Target | Validation* |
|---|---|---|
| Acid-Sensing | ASIC1a | PX |
| ASIC2a | PX | |
| ASIC3 | PX, QP | |
| Calcium, Voltage-Gated | Cav2.1/β4/α2δ1 | IWQ, MP, PX, QP |
| Cav2.2/β3/α2δ1 | IWQ, MP, PX, QP | |
| Cav3.2 | IWQ, PX | |
| Hyperpolarization-gated | HCN1 | PX |
| Ligand-Gated | GABAA (α3β3γ2) | |
| nAChR α7 | FLP, QP | |
| NMDA (NR1/NR2A) | FLP | |
| NMDA (NR1/NR2B) | FLP | |
| P2X1 | FLP | |
| P2X2 | FLP, QP | |
| P2X2/P2X3 | FLP | |
| P2X3 | FLP | |
| P2X4 | FLP, PX, QP | |
| P2X7 | QP | |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa3.1 | PX, QP | |
| Potassium, Voltage-Gated | Kv1.3 | IWQ |
| Kv1.4 | IWQ, QP | |
| Kv4.2/KChIP2.2 | MP, PX, QP | |
| Kv7.2/Kv7.3 | FLP, PX, QP | |
| Sodium, Voltage-Gated | Nav1.1 | IWQ, QP |
| Nav1.2 | IWQ, QP | |
| Nav1.3 | IWQ, PX, QP | |
| Nav1.7 | IWQ, PX, QP | |
| Nav1.8/β3 | FLP | |
| TRP | TRPA1 | FLP, MP |
| TRPM4 | FLP | |
| TRPM8 | FLP, MP, PX, QP | |
| TRPV1 | FLP, MP | |
| TRPV4 | FLP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Seizure-Convulsion Channel Panel™
Ion channels expressed in the CNS have been linked to inherited forms of epilepsy. Gain-of-function mutations in excitatory channels (e.g., voltage-gated sodium: Nav1.1, Nav1.2, and Nav1.3, voltage-gated calcium: Cav3.2, and hyperpolarization-gated: HCN1-2 channels) have been shown to cause persistent, depolarizing currents leading to hyper-excitability that facilitates epileptic seizures and convulsions. Hyper-excitability also may result from loss-of-function mutations in inhibitory channels (e.g., voltage-gated potassium: KCNQ2-5, calcium-dependent potassium: BK, and ligand-gated chloride: GABAA. Adverse neurological events may be caused by drug side-effects that mimic mutation-induced alterations in channel function. Conversely, antiepileptic drugs can act as antagonists of excitatory channels or as agonists of inhibitory channels. Thus, the ion channels in our seizure-convulsion panel are both potential therapeutic targets for treatment of hyper-excitability (e.g., seizure, pain, neurodegeneration, anxiety, migraine, and psychosis) or for anesthesia as well as targets for adverse events.
| Family | Target | Validation* |
|---|---|---|
| Calcium, Voltage-Gated | Cav2.1/β4/α2δ1 | IWQ, MP, PX, QP |
| Cav3.2 | IWQ, PX | |
| Hyperpolarization-gated | HCN1 | PX |
| HCN2 | IWQ, PX, QP | |
| Ligand-Gated | GABAA (a2β2γ2) | FLP |
| GABAA (α1/β2/γ2) | FLP | |
| NMDA (NR1/NR2A) | FLP | |
| NMDA (NR1/NR2B) | FLP | |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa2.2 | FLP, MP | |
| KCa2.3 | FLP | |
| Potassium, Voltage-Gated | Kv4.2/KChIP2.2 | MP, PX, QP |
| Kv7.2/Kv7.3 | FLP, PX, QP | |
| Kv7.2/Kv7.4 | PX | |
| Kv7.3/Kv7.5 | FLP, PX, QP | |
| Sodium, Voltage-Gated | Nav1.1 | IWQ, QP |
| Nav1.2 | IWQ, QP | |
| Nav1.3 | IWQ, PX, QP | |
| Nav1.6 | IWQ, PX, QP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Psychiatric Disorder Channel Panel™
Antipsychotic and antianxiety drugs that include ion channel targets are generally thought to modulate synaptic transmission in specific brain regions (e.g., the limbic system in schizophrenia, and both the limbic and brainstem reticular activating systems in anxiety). ChanTest’s Psychiatric Disorder Channel Panel™ includes neurotransmitter receptor channels that are important in anxiety (GABAA) and schizophrenia (NMDAR, and nAChRα7). Voltage-gated potassium channels (KCNQ2 – 5) that regulate excitability and are potential therapeutic targets for anxiety and schizophrenia also are included.
| Family | Target | Validation* |
|---|---|---|
| Calcium, Voltage-Gated | Cav1.3/β3/α2δ1 | FLP |
| Ligand-Gated | GABAA (a2β2γ2) | FLP |
| GABAA (a5β2γ2) | FLP, QP | |
| GABAA (α3β3γ2) | ||
| GABAA (α4β3γ2) | ||
| nAChR α7 | FLP, QP | |
| NMDA (NR1/NR2A) | FLP | |
| NMDA (NR1/NR2B) | FLP | |
| NMDA (NR1/NR2C) | FLP | |
| Potassium, Calcium-Activated | KCa2.1 | MP |
| KCa2.2 | FLP, MP | |
| KCa2.3 | FLP | |
| Potassium, Voltage-Gated | Kv7.2/Kv7.3 | FLP, PX, QP |
| Kv7.3/Kv7.5 | FLP, PX, QP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Pulmonary-Respiratory Channel Panel™
Increased airway resistance, symptomatic of diseases such as asthma and chronic obstructive pulmonary disease (COPD), can be treated by drugs that relax airway smooth muscle (e.g., muscarinic antagonists or adrenergic agonists, Figure 1) by decreasing cytoplasmic [Ca2+]. ChanTest’s Pulmonary-Respiratory Channel Panel™ contains several ion channels that regulate airway resistance. These include TRPV1 located in the sensory innervation of the epithelial layer. TRPV1 activation by environmental factors (e.g., temperature, pH, and irritants) triggers local release of neuropeptides that stimulate bronchoconstriction. The respiratory panel also includes airway regulatory channels located in the smooth muscle layer: GABAA receptors that conduct chloride current and cause muscle relaxation when activated, and two calcium-dependent potassium channels (KCa1.1 and KCa3.1) that also cause relaxation and bronchodilation when activated.
Increased resistance to flow in the lung blood vessels located in the submucosal layer is symptomatic of pulmonary hypertension. The Pulmonary-Respiratory Channel Panel™ contains both a voltage-gated potassium channel (Kv1.5) that promotes vasodilation and TRP channels (TRPC1 and TRPC6) that cause vasoconstriction when activated. These channels are potential therapeutic targets in pulmonary hypertension and upregulation in chronic hypoxia may contribute to hypoxic pulmonary hypertension .
| Family | Target | Validation* |
|---|---|---|
| Chloride | CFTR | IWQ, QP |
| Ligand-Gated | P2X4 | FLP, PX, QP |
| Potassium, Calcium-Activated | KCa1.1 | PX |
| KCa3.1 | PX, QP | |
| Potassium, Voltage-Gated | Kv1.3 | IWQ |
| Kv1.5 | IWQ, QP | |
| TRP | TRPA1 | FLP, MP |
| TRPC1 | MP | |
| TRPC6 | FLP, MP | |
| TRPV1 | FLP, MP | |
* MP: manual patch clamp - PX: PatchXpress® - QP: QPatch HT IWQ: IonWorks Quattro™ - FPR: FLIPRTETRA® | ||
Download: Ion Channel targets and current platform validation list.
For a quote or additional information, please email inquiries@chantest.com or call 216-332-1665.
