APPS November 2002 Meeting Abstract 1151


Neela Kotecha, Michael A. Hill, Microvascular Biology Group, School of Medical Sciences, RMIT University, Melbourne, Victoria 3083, Australia.

Pressure-induced arteriolar myogenic tone is associated with smooth muscle membrane depolarisation. Subsequent Ca2+ entry through voltage operated Ca2+ channels (VOCCs) has been widely implicated in the development/maintenance of myogenic tone. However, previous studies have provided disparate results regarding the exact contribution of voltage operated Cai2+ entry in the myogenic response. This could partly arise from participation of different Cai2+ entry/release mechanisms in the spatial and/or temporal components of a myogenic contraction. This study aimed to further define the source(s) of Cai2+ necessary for maintenance of myogenic tone.

Simultaneous recording of arteriole diameter with membrane potential (MP) revealed that pressure-induced depolarisation is not, itself, dependent on Ca2+ entry through VOCCs. The data obtained in the present study show that skeletal muscle arteriole tone is modulated by MP presumably by influencing Ca2+ entry through VOCCs. However, in arterioles maintained at 70 mm Hg, exposure to the VOCC inhibitors nifedipine (10 然) or verapamil (10 然) revealed that VOCCs contributed to some 30 % of maintained tone whilst the remainder of tone was resistant to these agents. In the presence of SERCA inhibitors (thapsigargin: 1 然 or CPA: 30 然) or the putative IP3 receptor blocker (2APB: 50 然) steady-state pressure-induced depolarisation and maintained tone were not affected by emptying of intracellular Ca2+ stores or inhibiting IP3 receptor-coupled mechanisms of Ca2+ entry. In contrast, combining protocols that inhibit exogenous Ca2+ entry (either through VOCCs or IP3 receptor-coupled mechanisms) with SERCA inhibitors resulted in complete loss of maintained tone.

The present studies suggest that Ca2+ supply during myogenic constriction requires interplay between the intracellular stores and Ca2+ influx from the extracellular space. It is postulated that store release of Ca2+ with the resultant influx of Ca2+, via both nifedipine and 2 APB sensitive pathways, form a dynamic unit to maintain myogenic tone.

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