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Responses of the sustained inward current to autonomic agonists in guinea-pig sino-atrial node pacemaker cells
| Content Provider | Scilit |
|---|---|
| Author | Toyoda, Futoshi Ding, Wei-Guang Matsuura, Hiroshi |
| Copyright Year | 2005 |
| Description | Journal: British Journal of Pharmacology 1 The present study was undertaken to examine the responses of the sustained inward current $(I_{st}$) to β‐adrenergic and muscarinic agonists in guinea‐pig sino‐atrial (SA) node cells using the whole‐cell patch‐clamp technique. $I_{st}$ was detected as the nicardipine (1 μM)‐sensitive inward current at potentials between ∼−80 and +20 mV in the presence of low concentration (0.1 mM) of extracellular $Ca^{2+}$, where the L‐type $Ca^{2+}$ current $(I_{Ca,L}$) was practically abolished. 2 β‐adrenergic agonist isoprenaline (ISO) in nanomolar concentrations not only increased the amplitude of $I_{st}$ but also shifted the membrane potential producing the peak amplitude $(V_{peak}$) to a negative direction by ∼15 mV without appreciably affecting potential range for the current activation. The stimulatory effect of ISO was concentration‐dependent with an $EC_{50}$ of 2.26 nM and the maximal effect (96.4±22.9% increase, n=6) was obtained at 100 nM ISO, when evaluated by the responses at −50 mV. 3 Bath application of acetylcholine (ACh) significantly inhibited $I_{st}$, which had been maximally augmented by 100 nM ISO; this inhibitory effect of ACh was concentration‐dependent with an $IC_{50}$ of 133.9 nM. High concentration (1000 nM) of ACh depressed basal $I_{st}$ by 10.5±2.0% (n=3). 4 In action potential clamp experiments, $I_{st}$ was also detected under control conditions and was markedly potentiated by exposure to ISO. 5 These results strongly suggest that $I_{st}$ not only contributes to the spontaneous action potentials of mammalian SA node cells but also plays a substantial role in mediating autonomic regulation of SA node pacemaker activity. British Journal of Pharmacology (2005) 144, 660–668. doi:10.1038/sj.bjp.0706101 |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576045/pdf |
| Ending Page | 668 |
| Page Count | 9 |
| Starting Page | 660 |
| e-ISSN | 14765381 |
| DOI | 10.1038/sj.bjp.0706101 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 144 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2005-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology Sustained Inward Current Slow Diastolic Depolarization Autonomic Regulation Action Potential Clamp |
| Content Type | Text |
| Resource Type | Article |
