Active force development by vascular smooth muscle in response to elevation of luminal pressure, or stretch, is termed the myogenic response, and is independent of neural, metabolic, hormonal and endothelial factors. The myogenic response is important for the local regulation of blood flow and for the generation of basal vascular tone. Mechanosensitive ion channels, especially non-selective cation channels (NSC) or chloride channels have been considered as possible candidates for transducing mechanical events into the contractile response of the cell. The aims of the present study are to confirm the existence of mechanosensitive ion channels in vascular smooth muscle cells at the single channel level and to investigate their characteristics.

The rabbits were terminally anaesthetized with pentobarbital sodium (50 mg kg^-1). We recorded single-channel currents from enzymatically dispersed pulmonary arterial smooth muscle cells (PASMCs) using the patch clamp technique. With 140 mM CsCl in the pipette solution, no channel opening was observed before applying negative pressure to the pipettes. Application of negative pressure to the pipettes induced channel opening in 100 of 2000 patches, indicating the presence of mechanosensitive ion channels. Open probability (NP_o) of the channels measured at -40 mV was increased from 0.12 ± 0.03 to 0.85 ± 0.08 when the negative pressure was increased from -10 cmH₂O to -30 cmH₂O (mean ± S.E.M., n = 5, P < 0.01, Student’s paired t test).

The single channel conductance was examined in excised inside-out patches under symmetrical ionic composition with 140 mM CsCl solutions both in pipettes and in the bath. The current-voltage relationship was linear between -80 mV and +80 mV, and the mean single channel conductance obtained from 15 patches was 34 ± 2.8 pS. When Cs⁺ in the pipette solution was replaced with a large impermeant cation such as N-methyl-D-glucamine (NMDG), inward current was abolished, whereas outward currents remained active. Replacing Cs⁺ with K⁺ or Na⁺ did not significantly affect the channel activity, except that the amplitude of inward current was slightly reduced in the presence of Na⁺. These results indicate that major mechanosensitive channels present in PASMCs are NSC channels. Pharmacological characteristics were tested. Gadolinium (30 µM), a blocker of NSC channels, blocked this channel (n = 5). Interestingly, DIDS (300 µM), a frequently used blocker of Cl^– channels, also blocked this channel (n = 5).

In conclusion, mechanosensitive ion channels present in PASMCs are NSC channels which can be blocked both by gadolinium and DIDS.