PMID- 10588929
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 128
IP  - 8
DP  - 1999 Dec
TI  - Bepridil differentially inhibits two delayed rectifier K(+) currents, I(Kr) and 
      I(Ks), in guinea-pig ventricular myocytes.
PG  - 1733-8
AB  - 1. We investigated the effects of bepridil on the two components of the delayed 
      rectifier K(+) current, i.e., the rapidly activating (I(Kr)) and the slowly 
      activating (I(Ks)) currents using tight-seal whole-cell patch-clamp techniques in 
      guinea-pig ventricular myocytes, under blockade of L-type Ca(2+) current with 
      nitrendipine (5 microM) or D600 (1 microM). 2. Bepridil decreased I(Ks) under 
      blockade of I(Kr) with E4031 (5 microM), in a concentration-dependent manner. The 
      concentration-dependent inhibition of I(Ks) by bepridil was fitted by a curve, 
      assuming one-to-one interactions between the channel and the drug molecule. The 
      concentration of half-maximal inhibition (IC(50)) was found to be 6.2 microM. 3. 
      The effect of bepridil on I(Kr) was assessed using an envelope-of-tails test. In 
      the control condition, a ratio of the tail current to the time-dependent current 
      measured during depolarization was large (>1) at shorter pulses (<200 ms), and it 
      decreased to a steady state value of approximately 0.4 with increases in the 
      pulse duration. Bepridil at a concentration of 2 microM did not decrease this 
      ratio at shorter pulses. 4. In a short-pulse (duration=50 ms) experiment that 
      largely activates I(Kr), the drug was found to block I(Kr) in a cooperative 
      manner (Hill coefficient=3.03) and the IC(50) was 13.2 microM. 5. These results 
      suggest that bepridil at a clinical therapeutic concentration ( approximately 2 
      microM) selectively blocks I(Ks) but does not inhibit I(Kr). This may relate to 
      the characteristic frequency-dependent effects of bepridil on the action 
      potential duration (APD), e.g., the non-reverse use-dependent prolongation of 
      APD.
FAU - Wang, J C
AU  - Wang JC
AD  - Department of Physiology, Oita Medical University, Hasama, Oita 879-5593, Japan. 
      kiyosue@oita.med.ac.jp
FAU - Kiyosue, T
AU  - Kiyosue T
FAU - Kiriyama, K
AU  - Kiriyama K
FAU - Arita, M
AU  - Arita M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 755BO701MA (Bepridil)
SB  - IM
MH  - Action Potentials/*drug effects
MH  - Animals
MH  - Bepridil/*pharmacology
MH  - Calcium Channel Blockers/*pharmacology
MH  - Guinea Pigs
MH  - Heart/*drug effects
MH  - Myocardium/cytology
MH  - Potassium Channels/*drug effects
PMC - PMC1571802
EDAT- 1999/12/10 09:00
MHDA- 2000/03/04 09:00
PMCR- 2000/12/01
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/12/10 09:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 0702959 [pii]
AID - 10.1038/sj.bjp.0702959 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1999 Dec;128(8):1733-8. doi: 10.1038/sj.bjp.0702959.