Airway smooth muscle cells express a variety of ion channels, e.g. L-type Ca2+ channels, Ca2+-activated Cl- channels (CaCC) and transient receptor potential channels (TRP), but unlike vascular smooth muscles, their role is still controversial (Janssen, 2012). The aim of this study was to investigate if these channels contribute to the contractile responses to carbachol (CCh) and histamine (His) in rabbit bronchial rings. New Zealand white rabbits were euthanized and the respiratory tree removed. Rings (length 2-4mm) from 3rd and 4th order bronchi were isolated and mounted in organ baths for isometric tension recording. Stock solutions of drugs were added directly to the bath and diluted to final concentrations. Data are presented as the mean±S.E.M, and statistical differences compared using Student’s paired t-test, taking p<0.05 as significant. When cumulative concentrations of CCh (0.1-10μM) were added, there was a concentration-dependent increase in tension (EC50=0.13μM; maximum response, Max=7.0±3.1 mN, n=6). When this was repeated in the presence of nifedipine (100nM), the responses were reduced throughout the CCh concentration range (Max=2.7±1.0mN, n=6, p<0.05), and EC50 was increased to 1.2μM. Similarly, His (0.1-10μM), caused a concentration-dependent increase in tension (EC50=1.3 μM; Max=9.2±2.1mN), which was also reduced by nifedipine (EC50= 1.1μM; Max=3.1±0.4mN, n=6, p<0.05). In contrast, the CaCC channel blocker, CaCCinh-A01 (10μM), had very little effect on CCh responses but markedly reduced His responses. For CCh it reduced Max slightly from 7.5±1.7 to 6.0±1.2mN (n=6, p<0.05), while EC50 was unaffected. However, for His, Max was reduced by CaCCinh-A01 from 7.1±1.9 to 3.6±0.8 mN (n=6, p<0.05) and EC50 increased from 1.3μM to 2.5μM. The fact that CaCCinh-A01 affected His, but not CCh, responses suggested that more than one depolarising pathway was available to activate the L-type Ca2+ channels. To investigate if this could have been via TRPC channels, we decided to test the effect of ML204, which blocks TRPC4 and TRPC5, selectivity compared to other TRP channels (Miller et al., 2011). ML204 (10μM) significantly reduced responses to both His and CCh. For CCh, it shifted the EC50 from 0.5µM to 3.1μM and reduced the response to 10μM from 10.2±1.5 to 6.6±1.1mN (n=6, p<0.05). The effects on His were greater, with EC50 shifting from 1.8 to 4.0μM and the response to 10μM decreasing from 4.9±0.6 to 1.7±0.2mN (n=6, p<0.05). In conclusion, L-type Ca2+ channels are likely to play a part in mediating responses to both His and CCh in rabbit bronchus, while CaCC seem to be involved only in the His responses. The fact that the novel TRPC4/5 blocker ML204 also reduced the responses to both agonists, provides preliminary evidence that TRPC4/5 may also be involved.