Sensitivity of cloned muscle, heart and neuronal voltage-gated sodium channels to block by polyamines
| Autor: | Theodore R. Cummins, Edward Moczydlowski, Li Ying Fu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Gene isoform
Spermidine Biophysics Spermine Endogeny CHO Cells Voltage-Gated Sodium Channels Biochemistry chemistry.chemical_compound Cricetulus Cricetinae Animals Humans Muscle Skeletal Ion channel Neurons Cell growth Sodium channel Heart Rats Cell biology Protein Subunits HEK293 Cells chemistry Intracellular Research Paper |
| Zdroj: | Channels. 6:41-49 |
| ISSN: | 1933-6969 1933-6950 |
| DOI: | 10.4161/chan.19001 |
| Popis: | Spermidine and spermine, are endogenous polyamines (PAs) that regulate cell growth and modulate the activity of numerous ion channel proteins. In particular, intracellular PAs are potent blockers of many different cation channels and are responsible for strong suppression of outward K (+) current, a phenomenon known as inward rectification characteristic of a major class of KIR K (+) channels. We previously described block of heterologously expressed voltage-gated Na (+) channels (NaV) of rat muscle by intracellular PAs and PAs have recently been found to modulate excitability of brain neocortical neurons by blocking neuronal NaV channels. In this study, we compared the sensitivity of four different cloned mammalian NaV isoforms to PAs to investigate whether PA block is a common feature of NaV channel pharmacology. We find that outward Na (+) current of muscle (NaV 1.4), heart (NaV 1.5), and neuronal (NaV 1.2, NaV 1.7) NaV isoforms is blocked by PAs, suggesting that PA metabolism may be linked to modulation of action potential firing in numerous excitable tissues. Interestingly, the cardiac NaV 1.5 channel is more sensitive to PA block than other isoforms. Our results also indicate that rapid binding of PAs to blocking sites in the NaV 1.4 channel is restricted to access from the cytoplasmic side of the channel, but plasma membrane transport pathways for PA uptake may contribute to long-term NaV channel modulation. PAs may also play a role in drug interactions since spermine attenuates the use-dependent effect of the lidocaine, a typical local anesthetic and anti-arrhythmic drug. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|