Tiapamil reduces the calcium inward current of isolated smooth muscle cells. Dependence on holding potential and pulse frequency

Abstract

The calcium currents (I Ca) of isolated smooth muscle cells (urinary bladder of the guinea-pig) were analyzed at 35°C and 3.6 mM [Ca] 0. The whole cells were voltage-clamped with a single patch electrode which was filled with 150 mM CsCl in order to block potassium outward currents. Tiapamil reduced I Ca at concentrations between 1 μM (threshold) and 0.5 mM (complete block). Administration of 10 μM tiapamil at rest reduced I Ca by 10% (‘initial block’). Repetitive depolarizations (140 ms long pulses to −5 mV, applied at 1 Hz) reduced I Ca further in a beat-to-beat fashion. This ‘conditioned block’ developed with a faster time course and to a greater extent when the stimulation frequency was increased and when the holding potentials were set to more positive levels. Reduction of I Ca by tiapamil was facilitated by more positive and attenuated by more negative holding potentials. The influence of holding potential and pulse frequency on the tiapamil effect is discussed in terms of the ‘modulated receptor hypothesis’.