HCN3 Activators
HCN3 Activators consist of a variety of chemical compounds that enhance the functional activity of HCN3 channels, primarily through the modulation of intracellular cyclic nucleotide levels. Forskolin, by directly stimulating adenylate cyclase, raises cAMP levels, which in turn activates PKA; the phosphorylation by PKA increases the open probability of HCN3, thus enhancing its pacemaker current. Similarly, Milrinone and Cilostamide, by inhibiting phosphodiesterase 3, prevent cAMP degradation, leading to PKA-mediated phosphorylation and increased HCN3 activity. IBMX, another phosphodiesterase inhibitor, elevates cAMP levels non-selectively, achieving the same end. Conversely, ZD7288, while typically an inhibitor, under certain dosages stabilizes HCN3 in its open state, paradoxically enhancing its current. Nicorandil, acting as a nitric oxide donor, may indirectly influence HCN3 activity via cGMP-cAMP pathway interactions. Dibutyryl-cAMP, a stable cAMP analog, bypasses the need for adenylate cyclase activation, directly activating PKA and enhancing HCN3 activity.
Vinpocetine, Sildenafil, SKF-94120, Rolipram, and Anagrelide all facilitate increased cyclic nucleotide levels, albeit via different mechanisms. Vinpocetine inhibits phosphodiesterase 1, while Sildenafil focuses on phosphodiesterase 5, both leading to cAMP and cGMP accumulation; this buildup can indirectly enhance HCN3 activity through PKA phosphorylation. SKF-94120 boosts cAMP directly, leading to a similar activation of PKA and subsequent phosphorylation of HCN3, thereby increasing its pacemaker efficacy. Rolipram, with its specificity for phosphodiesterase 4, increases cAMP in the brain, enhancing HCN3 activity in neuronal signaling through PKA. Anagrelide, another phosphodiesterase 3 inhibitor, raises cAMP levels and activates PKA, culminating in the upregulation of HCN3 channel activity. Collectively, these compounds enhance the functional activity of HCN3 by converging on the cAMP-PKA signaling axis and ensuring the phosphorylation and activation of HCN3 channels, crucial for their role in cardiac and neuronal rhythmicity without altering their expression levels.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Forskolin | 66575-29-9 | sc-3562 sc-3562A sc-3562B sc-3562C sc-3562D | 5 mg 50 mg 1 g 2 g 5 g | $78.00 $153.00 $740.00 $1413.00 $2091.00 | 73 | |
Forskolin directly stimulates adenylate cyclase, leading to an increase in cAMP levels. Elevated cAMP activates PKA, which can phosphorylate the HCN3 channel, resulting in an increased probability of channel opening and thus enhancing the functional activity of HCN3 by increasing its pacemaker current. | ||||||
Milrinone | 78415-72-2 | sc-201193 sc-201193A | 10 mg 50 mg | $165.00 $697.00 | 7 | |
Milrinone is a phosphodiesterase 3 inhibitor that prevents degradation of cAMP, indirectly leading to increased activity of PKA. PKA phosphorylation of HCN3 channels results in their enhanced activity, contributing to their role in cardiac and neuronal rhythmicity. | ||||||
Cilostamide (OPC 3689) | 68550-75-4 | sc-201180 sc-201180A | 5 mg 25 mg | $92.00 $357.00 | 16 | |
Cilostamide inhibits phosphodiesterase 3, leading to increased cAMP levels in cells. This accumulation of cAMP activates PKA, which in turn can enhance the activity of HCN3 channels by phosphorylation, increasing their contribution to cardiac pacemaking and neuronal excitability. | ||||||
IBMX | 28822-58-4 | sc-201188 sc-201188B sc-201188A | 200 mg 500 mg 1 g | $260.00 $350.00 $500.00 | 34 | |
IBMX is a non-selective inhibitor of phosphodiesterases, increasing intracellular cAMP levels. This rise in cAMP activates PKA, which can phosphorylate and enhance the activity of HCN3 channels, therefore augmenting their role in generating rhythmic electrical activity in the heart and brain. | ||||||
Nicorandil | 65141-46-0 | sc-200995 sc-200995B sc-200995A sc-200995C | 50 mg 100 mg 250 mg 1 g | $57.00 $98.00 $240.00 $500.00 | 4 | |
Nicorandil opens ATP-sensitive potassium channels and also acts as a nitric oxide donor. The nitric oxide component can stimulate guanylyl cyclase, increasing cGMP levels which may interact with cAMP signaling pathways and potentially enhance the activity of HCN3 channels indirectly. | ||||||
Dibutyryl-cAMP | 16980-89-5 | sc-201567 sc-201567A sc-201567B sc-201567C | 20 mg 100 mg 500 mg 10 g | $47.00 $136.00 $492.00 $4552.00 | 74 | |
Db-cAMP is a cAMP analog that is resistant to degradation by phosphodiesterases. It diffuses into cells and activates PKA. PKA phosphorylates HCN3 channels, enhancing their activity and increasing their pacemaker current, which is crucial for their role in cardiac and neuronal rhythmicity. | ||||||
Vinpocetine | 42971-09-5 | sc-201204 sc-201204A sc-201204B | 20 mg 100 mg 15 g | $55.00 $214.00 $2400.00 | 4 | |
Vinpocetine is a phosphodiesterase 1 inhibitor, leading to increased cAMP and cGMP levels. Through the cAMP pathway, it can activate PKA, which may enhance HCN3 channel activity by phosphorylation, thus supporting their function in controlling rhythmic electrical activity. | ||||||
Rolipram | 61413-54-5 | sc-3563 sc-3563A | 5 mg 50 mg | $77.00 $216.00 | 18 | |
Rolipram is a selective inhibitor of phosphodiesterase 4, which leads to increased cAMP levels in the brain. The increased cAMP levels activate PKA, which can enhance the activity of HCN3 channels by phosphorylation, influencing their role in neuronal signaling. | ||||||
Anagrelide | 68475-42-3 | sc-491875 | 25 mg | $150.00 | ||
Anagrelide inhibits phosphodiesterase 3, leading to increased cAMP levels. The elevated cAMP activates PKA, which may enhance the activity of HCN3 channels. | ||||||