Differential response of DPI-modified cardiac Na+ channels to antiarrhythmic drugs : no flicker blockade by lidocaine
Elementary Na+ currents were recorded in cell-attached patches from short-time cultured neonatal cardiocytes in order to test the hypothesis whether the open state of DPI-modified, noninactivating cardiac Na+ channels is basically sensitive to blocking drug molecules such as antiarrhythmics. Lidocaine (300 mumol/liter) effectively reduced the open probability of cardiac Na+ channels and, at a stimulation rate of 1 Hz, depressed the reconstructed macroscopic peak INa to 40 +/- 3.5% of the predrug value. The same drug concentration failed to influence DPI-modified Na+ channels. Their open state proved almost insensitive to lidocaine. tau open decreased only slightly to 85 +/- 2%. Still more importantly, the number of transitions between the conducting and a nonconducting configuration did not increase. At -40 mV, lidocaine may interfere with the open state with an association rate constant of 1.3 x 10(5) mol-1 sec-1 which is about two orders of magnitude smaller than the rate constant obtained with propafenone or prajmalium. Moreover, propafenone (10-20 mumol/liter) or prajmalium (30 mumol/liter) led to a tremendous increase in the number of transitions between the open and a nonconducting configuration. Lidocaine also failed to evoke a fast flicker blockade with reaction kinetics in the microsecond range. It is concluded that DPI-modified cardiac Na+ channels discriminate between lidocaine and other antiarrhythmic drugs. As a tentative explanation, this might be indicative for multiple binding sites for those drugs in cardiac Na+ channels.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
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| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:126 |
|---|---|
| Enthalten in: |
The Journal of membrane biology - 126(1992), 3 vom: 01. März, Seite 257-63 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Benz, I [VerfasserIn] |
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| Themen: |
97730-95-5 |
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| Anmerkungen: |
Date Completed 18.08.1992 Date Revised 19.08.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM013024299 |
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|---|---|---|---|
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| 100 | 1 | |a Benz, I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential response of DPI-modified cardiac Na+ channels to antiarrhythmic drugs |b no flicker blockade by lidocaine |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 18.08.1992 | ||
| 500 | |a Date Revised 19.08.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Elementary Na+ currents were recorded in cell-attached patches from short-time cultured neonatal cardiocytes in order to test the hypothesis whether the open state of DPI-modified, noninactivating cardiac Na+ channels is basically sensitive to blocking drug molecules such as antiarrhythmics. Lidocaine (300 mumol/liter) effectively reduced the open probability of cardiac Na+ channels and, at a stimulation rate of 1 Hz, depressed the reconstructed macroscopic peak INa to 40 +/- 3.5% of the predrug value. The same drug concentration failed to influence DPI-modified Na+ channels. Their open state proved almost insensitive to lidocaine. tau open decreased only slightly to 85 +/- 2%. Still more importantly, the number of transitions between the conducting and a nonconducting configuration did not increase. At -40 mV, lidocaine may interfere with the open state with an association rate constant of 1.3 x 10(5) mol-1 sec-1 which is about two orders of magnitude smaller than the rate constant obtained with propafenone or prajmalium. Moreover, propafenone (10-20 mumol/liter) or prajmalium (30 mumol/liter) led to a tremendous increase in the number of transitions between the open and a nonconducting configuration. Lidocaine also failed to evoke a fast flicker blockade with reaction kinetics in the microsecond range. It is concluded that DPI-modified cardiac Na+ channels discriminate between lidocaine and other antiarrhythmic drugs. As a tentative explanation, this might be indicative for multiple binding sites for those drugs in cardiac Na+ channels | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Sodium Channels |2 NLM | |
| 650 | 7 | |a DPI 201-106 |2 NLM | |
| 650 | 7 | |a 97730-95-5 |2 NLM | |
| 650 | 7 | |a Lidocaine |2 NLM | |
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| 700 | 1 | |a Kohlhardt, M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of membrane biology |d 1969 |g 126(1992), 3 vom: 01. März, Seite 257-63 |w (DE-627)NLM000006726 |x 1432-1424 |7 nnns |
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