Both L- and T-type calcium channels are present in the heart. In cardiac myocytes L-type calcium channels are blocked by the classical calcium channel blockers, while T-type calcium channels are thought to be insensitive to these drugs and to be selectively blocked by mibefradil. We aimed to compare the T/L calcium channel blocking selectivity of several calcium channel blockers by evaluating their effects on both components evoked in the same cell from a holding potential corresponding to the normal physiological value (-90mV). Currents were recorded in single patch-clamped guinea-pig ventricular myocytes, superfused with a Na(+)- and K(+)-free solution to abolish overlapping currents. Two dihydropyridines (amlodipine and lacidipine), verapamil diltiazem and mibefradil were tested; for each compound concentrations equieffective on L-type Ca(2+) current were used. All calcium channel blockers, at concentrations blocking less than 30% of L-type Ca(2+) current, inhibited a significant amount of T-type Ca(2+) current, varying from 0.8% (diltiazem) to 28% (mibefradil). We calculated for each compound the T/L ratio. As expected, mibefradil showed the highest T selectivity; lacidipine and diltiazem resulted to be L selective. Verapamil and amlodipine were not selective. Thus, the calcium channel blockers can be differentiated on the basis of their T/L selectivity.

SELECTIVITY OF DIFFERENT CALCIUM ANTAGONISTS ON T- AND L-TYPE CALCIUM CURRENTS IN GUINEA-PIG VENTRICULAR MYOCYTES / P. DE PAOLI; E. CERBAI; B. KOIDL; M. KIRCHENGAST; L. SARTIANI; A. MUGELLI.. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - STAMPA. - 46(2002), pp. 491-497. [10.1016/S1043661802002360]

SELECTIVITY OF DIFFERENT CALCIUM ANTAGONISTS ON T- AND L-TYPE CALCIUM CURRENTS IN GUINEA-PIG VENTRICULAR MYOCYTES.

CERBAI, ELISABETTA;SARTIANI, LAURA;MUGELLI, ALESSANDRO
2002

Abstract

Both L- and T-type calcium channels are present in the heart. In cardiac myocytes L-type calcium channels are blocked by the classical calcium channel blockers, while T-type calcium channels are thought to be insensitive to these drugs and to be selectively blocked by mibefradil. We aimed to compare the T/L calcium channel blocking selectivity of several calcium channel blockers by evaluating their effects on both components evoked in the same cell from a holding potential corresponding to the normal physiological value (-90mV). Currents were recorded in single patch-clamped guinea-pig ventricular myocytes, superfused with a Na(+)- and K(+)-free solution to abolish overlapping currents. Two dihydropyridines (amlodipine and lacidipine), verapamil diltiazem and mibefradil were tested; for each compound concentrations equieffective on L-type Ca(2+) current were used. All calcium channel blockers, at concentrations blocking less than 30% of L-type Ca(2+) current, inhibited a significant amount of T-type Ca(2+) current, varying from 0.8% (diltiazem) to 28% (mibefradil). We calculated for each compound the T/L ratio. As expected, mibefradil showed the highest T selectivity; lacidipine and diltiazem resulted to be L selective. Verapamil and amlodipine were not selective. Thus, the calcium channel blockers can be differentiated on the basis of their T/L selectivity.
46
491
497
P. DE PAOLI; E. CERBAI; B. KOIDL; M. KIRCHENGAST; L. SARTIANI; A. MUGELLI.
File in questo prodotto:
File Dimensione Formato  
DePaoli_PharmRes_2002.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: DRM non definito
Dimensione 110.08 kB
Formato Adobe PDF
110.08 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/21055
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 31
social impact